RESUMO
We recently reported that RNAi-mediated off-target effects are important drivers of the hepatotoxicity observed for a subset of GalNAc-siRNA conjugates in rodents, and that these findings could be mitigated by seed-pairing destabilization using a single GNA nucleotide placed within the seed region of the guide strand. Here, we report further investigation of the unique and poorly understood GNA/RNA cross-pairing behavior to better inform GNA-containing siRNA design. A reexamination of published GNA homoduplex crystal structures, along with a novel structure containing a single (S)-GNA-A residue in duplex RNA, indicated that GNA nucleotides universally adopt a rotated nucleobase orientation within all duplex contexts. Such an orientation strongly affects GNA-C and GNA-G but not GNA-A or GNA-T pairing in GNA/RNA heteroduplexes. Transposition of the hydrogen-bond donor/acceptor pairs using the novel (S)-GNA-isocytidine and -isoguanosine nucleotides could rescue productive base-pairing with the complementary G or C ribonucleotides, respectively. GalNAc-siRNAs containing these GNA isonucleotides showed an improved in vitro activity, a similar improvement in off-target profile, and maintained in vivo activity and guide strand liver levels more consistent with the parent siRNAs than those modified with isomeric GNA-C or -G, thereby expanding our toolbox for the design of siRNAs with minimized off-target activity.
Assuntos
Adenosina/química , Citidina/química , Glicóis/química , Guanosina/química , Oligorribonucleotídeos/química , RNA de Cadeia Dupla/química , RNA Interferente Pequeno/química , Acetilgalactosamina , Oxirredutases do Álcool/antagonistas & inibidores , Oxirredutases do Álcool/genética , Oxirredutases do Álcool/metabolismo , Animais , Pareamento de Bases , Células COS , Chlorocebus aethiops , Dimetilformamida/análogos & derivados , Dimetilformamida/química , Etilaminas/química , Feminino , Hepatócitos/citologia , Hepatócitos/metabolismo , Ligação de Hidrogênio , Camundongos , Camundongos Endogâmicos C57BL , Oligorribonucleotídeos/genética , Oligorribonucleotídeos/metabolismo , Compostos Organofosforados/química , Pré-Albumina/antagonistas & inibidores , Pré-Albumina/genética , Pré-Albumina/metabolismo , Cultura Primária de Células , Estabilidade de RNA , RNA de Cadeia Dupla/genética , RNA de Cadeia Dupla/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismoRESUMO
MiR-29a belongs to one of the subtypes of miRNAs known as non-coding single-stranded RNAs and is preferentially expressed in normal tissues. B7-H3, a member of the B7/CD28 immunoglobulin superfamily, was shown to be overexpressed in several solid malignant tumors, including colon cancer. In addition, it is associated with tumor progression and poor prognosis. We used immunohistochemical and Western blotting to assess B7-H3 protein expression levels in colon cancer and adjacent normal tissues and then compared their relationships with clinicopathological factors. Quantitative real-time reverse-transcription PCR was used to assess B7-H3 and miRNA-29a mRNA expression levels, and then their relationship and clinical significance were evaluated. In addition, colon cancer Caco-2 cells, which constitutively overexpress B7-H3, were transfected with lentivirus particles for miR-29a upregulation. Invasion and migration assays were carried out in vitro along with the establishment of a subcutaneous xenograft model in vivo to determine the role of miRNA-29a in colon cancer progression. The B7-H3 protein showed elevated expression in colon carcinoma and was relevant to TNM staging, lymph node metastasis, and reduced survival. Meanwhile, miR-29a was preferentially expressed in normal colon tissues, while B7-H3 transcript levels had no marked differences between tumor and normal tissue specimens. In vitro, miR-29a upregulation resulted in reduced B7-H3 expression. Furthermore, miR-29a upregulation reduced the invasive and migratory abilities of colon carcinoma cells. In animal models, upregulation of miR-29a slowed down the growth of subcutaneous xenotransplanted tumors and resulted in prolonged survival time. MiR-29a downregulates B7-H3 expression and accordingly inhibits colon cancer progression, invasion, and migration, indicating miR-29a and B7-H3 might represent novel molecular targets for advanced immunotherapy in colon cancer.
Assuntos
Antígenos B7/genética , Neoplasias do Colo/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Idoso , Idoso de 80 Anos ou mais , Animais , Antígenos B7/metabolismo , Células CACO-2 , Movimento Celular , Proliferação de Células , Neoplasias do Colo/metabolismo , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Progressão da Doença , Feminino , Humanos , Metástase Linfática , Masculino , Camundongos Endogâmicos BALB C , MicroRNAs/agonistas , MicroRNAs/antagonistas & inibidores , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Oligorribonucleotídeos/genética , Oligorribonucleotídeos/metabolismo , Transdução de Sinais , Análise de Sobrevida , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Understanding the underlying mechanisms of pediatric osteosarcoma (OS) migration and invasion is important for prognosis and treatment. We tried to measure the expression of long non-coding RNA HLA complex group 18 (HCG18) in OS and reveal its function in the malignant behaviors of OS cells. This study detected the expression of HCG18, miR-188-5p and forkhead box C1 (FOXC1) in OS tissues and cell lines by quantitative real-time PCR (qRT-PCR). The relevance between miR-188-5p and HCG18 or FOXC1 was affirmed by dual-luciferase reporter (DLR) assay. Cell viability was analyzed by MTT assay. Transwell assay was utilized to test cell invasion and migration. FOXC1 protein expression was detected by western blot. HCG18 expression was elevated in OS tissues, and enhanced HCG18 expression was related to metastasis. HCG18 silencing repressed the viability, migration and invasion of OS cells. Moreover, HCG18 interacted with miR-188-5p. MiR-188-5p up-regulation repressed cell viability, invasion and migration in OS cells. FOXC1, a known target of miR-188-5p, was negatively modulated by miR-188-5p. Furthermore, miR-188-5p inhibition or FOXC1 over-expression partially abolished the reduced of cell viability, invasion and migration mediated by HCG18 silencing in OS cell lines. This study revealed that HCG18 knockdown repressed the viability, invasion and migration of OS cells by targeting miR-188-5p and regulating FOXC1 expression. Thus, HCG18/ miR-188-5p/FOX may be a hopeful target for OS therapy.
Assuntos
Neoplasias Ósseas/genética , Fatores de Transcrição Forkhead/genética , MicroRNAs/genética , Osteoblastos/metabolismo , Osteossarcoma/genética , RNA Longo não Codificante/genética , Adolescente , Pareamento de Bases , Sequência de Bases , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Linhagem Celular , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Sobrevivência Celular , Criança , Pré-Escolar , Feminino , Fatores de Transcrição Forkhead/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , MicroRNAs/agonistas , MicroRNAs/antagonistas & inibidores , MicroRNAs/metabolismo , Invasividade Neoplásica , Oligorribonucleotídeos/genética , Oligorribonucleotídeos/metabolismo , Osteoblastos/patologia , Osteossarcoma/metabolismo , Osteossarcoma/patologia , RNA Longo não Codificante/agonistas , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Adulto JovemRESUMO
AIMS/HYPOTHESIS: The incidence of type 1 diabetes is increasing more rapidly than can be explained by genetic drift. Viruses may play an important role in the disease, as they seem to activate the 2'-5'-linked oligoadenylate (2'-5'A) pathway of the innate antiviral immune system. Our aim was to investigate this possibility. METHODS: Innate antiviral immune pathways were searched for type 1 diabetes-associated polymorphisms using genome-wide association study data. SNPs within ±250kb flanking regions of the transcription start site of 64 genes were examined. These pathways were also investigated for type 1 diabetes-associated RNA expression profiles using laser-dissected islets from two to five tissue sections per donor from the Diabetes Virus Detection (DiViD) study and the network of Pancreatic Organ Donors (nPOD). RESULTS: We found 27 novel SNPs in genes nominally associated with type 1 diabetes. Three of those SNPs were located upstream of the 2'-5'A pathway, namely SNP rs4767000 (p = 1.03 × 10-9, OR 1.123), rs1034687 (p = 2.16 × 10-7, OR 0.869) and rs739744 (p = 1.03 × 10-9, OR 1.123). We also identified a large group of dysregulated islet genes in relation to type 1 diabetes, of which two were novel. The most aberrant genes were a group of IFN-stimulated genes. Of those, the following distinct pathways were targeted by the dysregulation (compared with the non-diabetic control group): OAS1 increased by 111% (p < 1.00 × 10-4, 95% CI -0.43, -0.15); MX1 increased by 142% (p < 1.00 × 10-4, 95% CI -0.52, -0.22); and ISG15 increased by 197% (p = 2.00 × 10-4, 95% CI -0.68, -0.18). CONCLUSIONS/INTERPRETATION: We identified a genetic predisposition in the 2'-5'A pathway that potentially contributes to dysregulation of the innate antiviral immune system in type 1 diabetes. This study describes a potential role for the 2'-5'A pathway and other components of the innate antiviral immune system in beta cell autoimmunity.
Assuntos
Nucleotídeos de Adenina/genética , Diabetes Mellitus Tipo 1/genética , Regulação da Expressão Gênica/fisiologia , Predisposição Genética para Doença , Imunidade Inata/genética , Oligorribonucleotídeos/genética , Polimorfismo de Nucleotídeo Único/genética , Viroses/imunologia , Adulto , Antivirais/uso terapêutico , Diabetes Mellitus Tipo 1/virologia , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , RNA Mensageiro/genética , Proteínas de Ligação a RNA/genética , Viroses/tratamento farmacológico , Adulto JovemRESUMO
Evidence indicates that macrophages play an important role in the immune system. Therefore, research involving inflammatory and oxidative stress responses in macrophages is of great significance. Many factors contribute to inflammation and oxidative stress, including Salmonella. We investigated the effect of the miR-139-5p/TRAF6 axis on the inflammatory and oxidative stress responses of Salmonella -infected macrophages. Our findings revealed that miR-139-5p decreased IL-1ß and TNF-α levels to inhibit Salmonella-induced inflammatory responses in the RAW264.7 macrophage cell line. Furthermore, miR-139-5p inhibited Salmonella-induced oxidative stress by strengthening SOD, CAT and GSH-PX activity, as well as lowering the malondialdehyde level in the RAW264.7 macrophages cell line. Subsequently, it was verified that TRAF6 was a downstream target of miR-139-5p in RAW264.7 cells. Rescue assays indicated that the over-expression of miR-139-5p inhibits the effects of TRAF6 on inflammatory and oxidative stress responses including Salmonella infection in RAW264.7 cells. To our knowledge, this study is the first to verify that miR-139-5p inhibits inflammatory and oxidative stress responses of Salmonella-infected macrophages through regulating TRAF6. This discovery may offer new insights on inflammatory and oxidative stress responses in macrophages.
Assuntos
Interações Hospedeiro-Patógeno/genética , MicroRNAs/genética , Salmonella typhimurium/genética , Fator 6 Associado a Receptor de TNF/genética , Animais , Pareamento de Bases , Sequência de Bases , Catalase/genética , Catalase/metabolismo , Regulação da Expressão Gênica , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Lipopolissacarídeos/farmacologia , Malondialdeído/metabolismo , Camundongos , MicroRNAs/agonistas , MicroRNAs/antagonistas & inibidores , MicroRNAs/metabolismo , Mimetismo Molecular , Oligorribonucleotídeos/genética , Oligorribonucleotídeos/metabolismo , Estresse Oxidativo , Células RAW 264.7 , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/crescimento & desenvolvimento , Salmonella typhimurium/metabolismo , Transdução de Sinais , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Fator 6 Associado a Receptor de TNF/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Atherosclerosis is a chronic inï¬ammatory disease, and it's the leading cause of death worldwide. Dysregulation of microRNAs (miRNAs) has been found to be associated with atherosclerosis. miR-520c-3p has been implicated in several types of cancer. However, little is known about the role of miR-520c-3p in atherosclerosis. In this study, we found that miR-520c-3p agomir decreased atherosclerotic plaque size, collagen content, the quantity of PCNA-positive cell and RelA/p65 expression of vascular smooth muscle cells (VSMCs) in the aortic valve of apoE-/- mice in vivo. The possible mechanisms of the protective effects of miR-520c-3p on atherosclerotic mice were then investigated in VSMCs. in vitro experiments showed that miR-520c-3p expressions were significantly reduced in human aortic vascular smooth muscle cell (HASMCs) treated with platelet-derived growth factor (PDGF-BB). miR-520c-3p mimics repress PDGF-BB-mediated the proliferation, migration and decrease in the percentage of cells in G2/M phase, which was associated with downregulation of RelA/p65. Mechanistically, miRNA pull-down, luciferase reporter and mRNA stability assays confirmed miR-520c-3p mimics was able to directly target 3'-UTR of RelA/p65 mRNA and decreased half-life of RelA/p65 mRNA in HASMCs. Overexpression of RelA/p65 reversed the inhibition of cell proliferation induced by miR-520c-3p mimics in HASMCs. In conclusion, our findings suggest that miR-520c-3p inhibits PDGF-BB-mediated the proliferation and migration of HASMCs by targeting RelA/p65, which may provide potential therapeutic strategies in atherosclerosis treatment.
Assuntos
Aterosclerose/genética , MicroRNAs/genética , Miócitos de Músculo Liso/metabolismo , Placa Aterosclerótica/genética , Fator de Transcrição RelA/genética , Animais , Valva Aórtica/metabolismo , Valva Aórtica/patologia , Aterosclerose/metabolismo , Aterosclerose/patologia , Aterosclerose/terapia , Becaplermina/farmacologia , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Regulação da Expressão Gênica , Genes Reporter , Humanos , Luciferases/genética , Luciferases/metabolismo , Camundongos , Camundongos Knockout para ApoE , MicroRNAs/agonistas , MicroRNAs/antagonistas & inibidores , MicroRNAs/metabolismo , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/patologia , Oligorribonucleotídeos/genética , Oligorribonucleotídeos/metabolismo , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patologia , Placa Aterosclerótica/terapia , Cultura Primária de Células , Transdução de Sinais , Fator de Transcrição RelA/metabolismoRESUMO
BACKGROUND: MicroRNAs play a crucial role in diabetic peripheral neuropathic pain (DPNP). miR-590-3p is a novel miRNA and involved in multiple diseases. However, the pathological mechanism of miR-590-3p in DPNP needs to be elucidated. MATERIALS AND METHODS: The db/db mice and db/m mice were selected to mimic diabetes and control, respectively, for in vivo studies. The miR-590-3p agomir was injected into db/db mice and pain-related behavioral tests were performed. The interaction of miR-590-3p with target gene was confirmed by dual-luciferase reporter assay. The expression of target gene was determined by qRT-PCR and western blot assay. The levels of inflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: miR-590-3p was down-regulated in diabetic peripheral neuropathy mice. More importantly, miR-590-3p agomir alleviated pain-related behavior, reduced TNF-α, IL-1ß and IL-6 concentrations, and inhibited neural infiltration by immune cells in db/db mice. Interestingly, RAP1A was predicted to be the target of miR-590-3p by Targetscan, and was actually regulated by miR-590-3p. Finally, the rescue experiments proved that overexpression of RAP1A partially abrogated the suppressive impact of miR-590-3p on T cells proliferation and migration. CONCLUSION: miR-590-3p ameliorates DPNP via targeting RAP1A and inhibiting T cells infiltration, indicating that exogenous miR-590-3p may be a potential candidate for clinical treatment of DPNP.
Assuntos
Diabetes Mellitus Tipo 2/genética , Neuropatias Diabéticas/genética , MicroRNAs/genética , Neuralgia/genética , Linfócitos T/imunologia , Proteínas rap1 de Ligação ao GTP/genética , Animais , Antagomirs/genética , Antagomirs/metabolismo , Pareamento de Bases , Sequência de Bases , Movimento Celular , Proliferação de Células , Diabetes Mellitus Tipo 2/imunologia , Diabetes Mellitus Tipo 2/patologia , Neuropatias Diabéticas/imunologia , Neuropatias Diabéticas/patologia , Modelos Animais de Doenças , Gânglios Espinais/imunologia , Gânglios Espinais/patologia , Regulação da Expressão Gênica , Genes Reporter , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Luciferases/genética , Luciferases/metabolismo , Masculino , Camundongos , MicroRNAs/agonistas , MicroRNAs/antagonistas & inibidores , MicroRNAs/imunologia , Neuralgia/imunologia , Neuralgia/patologia , Neuralgia/prevenção & controle , Oligorribonucleotídeos/genética , Oligorribonucleotídeos/metabolismo , Transdução de Sinais , Linfócitos T/patologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia , Proteínas rap1 de Ligação ao GTP/imunologiaRESUMO
Asthma is considered as a general term for various chronic inflammatory diseases of the respiratory tract. Growing evidences have supported that microRNAs were involved in mediating cell proliferation, migration, and other cellular functions. MiR-149 has been found to take part in the development of various cancers. However, whether miR-149 participated in the proliferation and migration of transforming growth factor beta 1 (TGF-ß1)-induced airway smooth muscle cells was still unknown. In this study, the expression level of miR-149 in human airway smooth muscle cells (ASMCs) was decreased after TGF-ß1 treatment in vitro. Additionally, the over-expression of miR-149 obviously suppressed proliferation and migration in human ASMCs. Besides, we found that overexpression of miR-149 could inhibit the expression of transient receptor potential melastatin 7 (TRPM7) both in protein and gene levels. Furthermore, we demonstrated that miR-149 could inhibit the cell proliferation and migration in human ASMCs by targeting TRPM7 through modulating mitogen-activated protein kinases (MAPKs) signaling pathway. Taken together, we strongly supported that miR-149 might be a key inhibitor of asthma by targeting TRMP7. Therefore, our finding suggests a promising biomarker for the development of further targeted therapies for asthma.
Assuntos
MicroRNAs/genética , Miócitos de Músculo Liso/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/genética , Transdução de Sinais/genética , Canais de Cátion TRPM/genética , Fator de Crescimento Transformador beta1/farmacologia , Antagomirs/genética , Antagomirs/metabolismo , Pareamento de Bases , Sequência de Bases , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Regulação da Expressão Gênica , Células HEK293 , Humanos , MAP Quinase Quinase 4/genética , MAP Quinase Quinase 4/metabolismo , MicroRNAs/agonistas , MicroRNAs/antagonistas & inibidores , MicroRNAs/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/metabolismo , Oligorribonucleotídeos/genética , Oligorribonucleotídeos/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sistema Respiratório/citologia , Sistema Respiratório/efeitos dos fármacos , Sistema Respiratório/metabolismo , Canais de Cátion TRPM/metabolismo , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
BACKGROUND: Accumulating evidence has suggested that long noncoding RNAs (lncRNAs) are involved in the progression of types of human cancers. It has been known that exosomes can mediate cell-cell crosstalk by transferring lncRNAs in tumor progression. This study aimed to investigate the role of exosomal lncRNA HEIH on cisplatin (DDP) resistance in tongue squamous cell carcinoma (TSCC). METHODS: The expression of HEIH in human oral keratinocytes cell line (HOK), DDP-sensitive TSCC cell line (SCC4/S) and DDP-resistant TSCC cell line (SCC4/DDP) was measured. SCC4/S and SCC4/DDP cells were transfected with sh-HEIH to examine TSCC cell proliferation and apoptosis. The DDP-resistant exosomes were extracted and identified. The expression of miR3619-5p and TDGF in DDP-sensitive recipient cells was determined. The binding capacity between HEIH and miR3619-5p, along with miR3619-5p and TDGF was verified. RESULTS: HEIH expression was significantly upregulated in SCC4/DDP cells. Downregulation of HEIH inhibited DDP resistance and cell proliferation and promoted cell apoptosis. HEIH acted as a competing endogenous RNA (ceRNA) for miR3619-5p to upregulate HDGF expression. Exosomal HEIH promoted cell proliferation and drug resistance and inhibited cell apoptosis by sponging miR3169-5p and upregulating HDGF. CONCLUSION: Exosomal HEIH acted as a ceRNA for miR3619-5p to upregulate HDGF, thereby promoting DDP resistance in TSCC cells.
Assuntos
Antineoplásicos/farmacologia , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Células Epiteliais/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , Apoptose/genética , Pareamento de Bases , Sequência de Bases , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Células Epiteliais/patologia , Exossomos/efeitos dos fármacos , Exossomos/genética , Exossomos/metabolismo , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Genes Reporter , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Luciferases/genética , Luciferases/metabolismo , MicroRNAs/metabolismo , Oligorribonucleotídeos/genética , Oligorribonucleotídeos/metabolismo , RNA Longo não Codificante/metabolismo , Transdução de SinaisRESUMO
BACKGROUND: We recently identified 39 human microRNAs, which effectively suppress hepatitis B virus (HBV) replication in hepatocytes. Chronic HBV infection often results in active, hepatitis-related liver fibrosis; hence, we assessed whether any of these microRNAs have anti-fibrotic potential and predicted that miR-6133-5p may target several fibrosis-related genes. METHODS: The hepatic stellate cell line LX-2 was transfected with an miR-6133-5p mimic and subsequently treated with Transforming growth factor (TGF)-ß. The mRNA and protein products of the COL1A1 gene, encoding collagen, and the ACTA2 gene, an activation marker of hepatic stellate cells, were quantified. RESULTS: The expression of COL1A1 and ACTA2 was markedly reduced in LX-2 cells treated with miR-6133-5p. Interestingly, phosphorylation of c-Jun N-terminal kinase (JNK) was also significantly decreased by miR-6133-5p treatment. The expression of several predicted target genes of miR-6133-5p, including TGFBR2 (which encodes Transforming Growth Factor Beta Receptor 2) and FGFR1 (which encodes Fibroblast Growth Factor Receptor 1), was also reduced in miR-6133-5p-treated cells. The knockdown of TGFBR2 by the corresponding small interfering RNA greatly suppressed the expression of COL1A1 and ACTA2. Treatment with the JNK inhibitor, SP600125, also suppressed COL1A1 and ACTA2 expression, indicating that TGFBR2 and JNK mediate the anti-fibrotic effect of miR-6133-5p. The downregulation of FGFR1 may result in a decrease of phosphorylated Akt, ERK (extracellular signal-regulated kinase), and JNK. CONCLUSION: miR-6133-5p has a strong anti-fibrotic effect, mediated by inactivation of TGFBR2, Akt, and JNK.
Assuntos
Colágeno Tipo I/genética , Células Estreladas do Fígado/metabolismo , MAP Quinase Quinase 4/genética , MicroRNAs/genética , Proteínas Proto-Oncogênicas c-akt/genética , Receptor do Fator de Crescimento Transformador beta Tipo II/genética , Actinas/genética , Actinas/metabolismo , Antracenos/farmacologia , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Transformada , Proliferação de Células/efeitos dos fármacos , Colágeno Tipo I/metabolismo , Cadeia alfa 1 do Colágeno Tipo I , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/patologia , Regulação da Expressão Gênica , Células Estreladas do Fígado/citologia , Células Estreladas do Fígado/efeitos dos fármacos , Humanos , MAP Quinase Quinase 4/antagonistas & inibidores , MAP Quinase Quinase 4/metabolismo , MicroRNAs/agonistas , MicroRNAs/antagonistas & inibidores , MicroRNAs/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Oligorribonucleotídeos/genética , Oligorribonucleotídeos/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Receptor do Fator de Crescimento Transformador beta Tipo II/antagonistas & inibidores , Receptor do Fator de Crescimento Transformador beta Tipo II/metabolismo , Transdução de Sinais , Fator de Crescimento Transformador beta/farmacologiaRESUMO
Long non-coding RNA (lncRNA) ANRIL has been reported to be closely related to the relapse of multiple myeloma patients. However, the functional role and underlying mechanism of lncRNA ANRIL in multiple myeloma are not known. This study aims to investigate the biological function of lncRNA ANRIL in multiple myeloma. In this study, compared with normal tissues from healthy donors, lncRNA ANRIL and HIF-1α expressions were up-regulated in tumor tissues from multiple myeloma patients. miR-411-3p expression was down-regulated in tumor tissues from multiple myeloma patients. Besides, lncRNA ANRIL can interact with miR-411-3p. HIF-1α was confirmed to be a target of miR-411-3p. Correlation analysis showed that lncRNA ANRIL expression was negatively correlated with miR-411-3p expression. HIF-1α expression was negatively correlated with miR-411-3p expression. Further transfection experiments showed that knockdown of ANRIL or overexpression of miR-411-3p significantly inhibited cell proliferation, tumor formation ability and tumor stem cell like property, promoted cell apoptosis in vitro. Finally, miR-411-3p mimic reduced tumor volume, improved survival rate, suppressed malignant proliferation and tumor stem cell like property in U266 xenograft model. Our results demonstrate that lncRNA ANRIL mediated by miR-411-3p promotes the malignant proliferation and tumor stem cell like property of multiple myeloma through regulating HIF-1α.
Assuntos
Carcinogênese/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , MicroRNAs/genética , Mieloma Múltiplo/genética , Recidiva Local de Neoplasia/genética , RNA Longo não Codificante/genética , Animais , Apoptose/genética , Carcinogênese/metabolismo , Carcinogênese/patologia , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Camundongos , Camundongos Nus , MicroRNAs/agonistas , MicroRNAs/metabolismo , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/patologia , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Oligorribonucleotídeos/genética , Oligorribonucleotídeos/metabolismo , Plasmócitos/metabolismo , Plasmócitos/patologia , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/metabolismo , Transdução de Sinais , Análise de Sobrevida , Carga Tumoral , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Epithelial-mesenchymal transition (EMT) is an important contributor to drug resistance in ovarian cancer. The aims of this study were to explore the potential role of the miR-302 cluster in modulating EMT and cisplatin resistance in ovarian cancer. We used qRT-PCR and western blotting to show that miR-302 expression was lower in chemoresistant than in chemosensitive cells, and miR-302 was upregulated in chemosensitive, but not chemoresistant ovarian cancer cells in response to cisplatin treatment. We identified ATAD2 as a target of miR-302 and showed that ectopic expression of miR-302 increased cisplatin sensitivity and inhibited EMT and the invasiveness of cisplatin-resistant cells in vitro by targeting ATAD2. Knockdown of ATAD2 restored cisplatin sensitivity and reversed EMT/metastasis in cisplatin-resistant cells, as shown by western blotting and invasion/migration assays. The effect of miR-302 overexpression on EMT and invasiveness was mediated by the modulation of ß-catenin nuclear expression. Immunofluorescence analysis showed that ATAD2 overexpression reversed the miR-302-induced downregulation of nuclear ß-catenin in cisplatin resistant cells. A xenograft tumor model was used to show that miR-302 increases the antitumor effect of cisplatin in vivo. Taken together, these results identify a potential regulatory axis involving miR-302 and ATAD2 with a role in chemoresistance, indicating that activation of miR-302 or inactivation of ATAD2 could serve as a novel approach to reverse cisplatin resistance in ovarian cancer.
Assuntos
ATPases Associadas a Diversas Atividades Celulares/genética , Antineoplásicos/farmacologia , Carcinoma Epitelial do Ovário/genética , Cisplatino/farmacologia , Proteínas de Ligação a DNA/genética , Resistencia a Medicamentos Antineoplásicos/genética , MicroRNAs/genética , Neoplasias Ovarianas/genética , ATPases Associadas a Diversas Atividades Celulares/metabolismo , Animais , Antagomirs/genética , Antagomirs/metabolismo , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/metabolismo , Carcinoma Epitelial do Ovário/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Proteínas de Ligação a DNA/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/agonistas , MicroRNAs/antagonistas & inibidores , MicroRNAs/metabolismo , Oligorribonucleotídeos/genética , Oligorribonucleotídeos/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Transdução de Sinais , Carga Tumoral , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVE: Hepatic stellate cells (HSC) activation and proliferation mediated the pathogenic development of hepatic fibrosis (HF). However, the underlying mechanisms remain poorly understood. In this study, we aimed to investigate the miR-29a-3p and its effects on PIK3R3 expression in HF pathogenesis. METHODS: LX-2 cells treated with TGF-ß1 was used as the in vitro HF model. The expression of microRNAs and proteins in LX-2 cells were detected by quantitative RT-PCR and western blotting. Then, miR-29a-3p expression in LX-2 cells were altered via transfection with specific mimics or inhibitors, followed by cell proliferation measured through CCK-8, Edu staining and colony formation. The dual luciferase reporter assay was done to assess binding of miR-29a-3p with PIK3R3 gene sequences. Moreover, PIK3R3 gene overexpression in LX-2 cell was realized through transfection with recombinant pcDNA3.0-PIK3R3 plasmids. RESULTS: Successful establishment of cellular HF model was validated through the increased Col-I and a-SMA expression in TGF-ß1-treated LX-2 cells shown by qRT-PCR and Western blot. In such model, miR-29a-3p expression in LX-2 cells showed the greatest decrease among four candidate microRNAs in response to TGF-ß1 treatment. Also, miR-29a-3p directly binds with the 3' UTR region of the PIK3R3 gene to suppress its expression in LX-2 cells. Furthermore, PIK3R3 gene overexpression effectively abrogated the changes of LX-2 cell proliferation, AKT phosphorylation and Col-I and a-SMA expression caused by miR-29a-3p mimics. CONCLUSION: MiR-29a-3p regulates hepatic stellate cell proliferation and hepatic fibrosis pathogenesis by targeting PIK3R3 expression and modulating the PI-3K/AKT signaling.
Assuntos
Células Estreladas do Fígado/metabolismo , Cirrose Hepática/genética , MicroRNAs/genética , Fosfatidilinositol 3-Quinases/genética , Regiões 3' não Traduzidas , Actinas/genética , Actinas/metabolismo , Antagomirs/genética , Antagomirs/metabolismo , Pareamento de Bases , Sequência de Bases , Linhagem Celular Transformada , Proliferação de Células , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Regulação da Expressão Gênica , Genes Reporter , Células Estreladas do Fígado/efeitos dos fármacos , Células Estreladas do Fígado/patologia , Humanos , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Luciferases/genética , Luciferases/metabolismo , MicroRNAs/agonistas , MicroRNAs/antagonistas & inibidores , MicroRNAs/metabolismo , Modelos Biológicos , Oligorribonucleotídeos/genética , Oligorribonucleotídeos/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Fator de Crescimento Transformador beta1/farmacologiaRESUMO
Oligoribonucleotide (ORN) interference-PCR (ORNi-PCR) is a method in which PCR amplification of a target sequence is inhibited in a sequence-specific manner by the hybridization of an ORN with the target sequence. Previously, we reported that ORNi-PCR could detect nucleotide mutations in DNA purified from cultured cancer cell lines or genome-edited cells. In this study, we investigated whether ORNi-PCR can discriminate nucleotide differences and CpG methylation status in damaged DNA, such as tissue specimen DNA and bisulfite-treated DNA. First, we showed that ORNi-PCR could discriminate nucleotide differences in DNA extracted from acetone-fixed paraffin-embedded rat liver specimens or formalin-fixed paraffin-embedded human specimens. Rat whole blood specimens were compatible with ORNi-PCR for the same purpose. Next, we showed that ORNi-PCR could discriminate CpG methylation status in bisulfite-treated DNA. These results demonstrate that ORNi-PCR can discriminate nucleotide differences and CpG methylation status in multiple types of DNA samples. Thus, ORNi-PCR is potentially useful in a wide range of fields, including molecular biology and medical diagnosis.
Assuntos
Ilhas de CpG , Metilação de DNA , Reação em Cadeia da Polimerase/métodos , Acetona/química , Animais , Linhagem Celular , Formaldeído/química , Humanos , Fígado/metabolismo , Oligorribonucleotídeos/genética , Inclusão em Parafina , Ratos , Ratos Sprague-Dawley , Sulfitos/química , Fixação de TecidosRESUMO
It has been reported microRNA-301b (miR-301b) was involved in the tumorigenesis of some cancers, but it has not been investigated in cervical carcinoma yet. In this study, miR-301b was found significantly upregulated in cervical carcinoma, and patients with high miR-301b expression had a shorter overall survival. When miR-301b was knocked down in cervical carcinoma cells, the cell growth could be significantly abolished. Our further studies showed miR-301b targeted RNF38, and inhibited its expression in cervical carcinoma cells. Moreover, RNF38 was found downregulated in cervical carcinoma, and miR-301b expression in cervical tissues was found negatively correlated with RNF38 expression. In addition, overexpression of RNF38 significantly inhibited cervical carcinoma cell growth, but overexpression of miR-301b suppressed RNF38-induced cell growth inhibition in cervical carcinoma. Collectively, this study suggested miR-301b could be a novel target for cervical carcinoma treatment.
Assuntos
Adenocarcinoma/genética , Carcinoma de Células Escamosas/genética , Proteínas de Transporte/genética , MicroRNAs/genética , Neoplasias do Colo do Útero/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Antagomirs/genética , Antagomirs/metabolismo , Pareamento de Bases , Sequência de Bases , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Proteínas de Transporte/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Colo do Útero/metabolismo , Colo do Útero/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática , MicroRNAs/agonistas , MicroRNAs/antagonistas & inibidores , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Oligorribonucleotídeos/genética , Oligorribonucleotídeos/metabolismo , Transdução de Sinais , Análise de Sobrevida , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologiaRESUMO
The dysregulation of miR-532-5p is involved in the development of several cancers. Nevertheless, the roles of miR-532-5p in osteosarcoma (OS) have yet to be illuminated. In the present study, we found that miR-532-5p was significantly downregulated in both OS tissues and cell lines. The low level of miR-532-5p was associated with advance clinical stage and poor overall survival in patient with OS. The functional experiments implied that upregulation of miR-532-5p restrained OS U2OS cell growth and metastatic ability in vitro; induced apoptosis, and impaired OS cell growth in vivo. Mechanistically, chemokine (C-X-C Motif) ligand 2 (CXCL2) was proved as a target gene of miR-532-5p. The inhibitory effects of miR-532-5p on OS cell were rescued by CXCL2 overexpression. Altogether, we demonstrated that miR-532-5p exerted tumor-inhibitory functions in OS cell via regulating CXCL2.
Assuntos
Neoplasias Ósseas/genética , Quimiocina CXCL2/genética , MicroRNAs/genética , Osteossarcoma/genética , Adolescente , Adulto , Antagomirs/genética , Antagomirs/metabolismo , Apoptose/genética , Pareamento de Bases , Sequência de Bases , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/mortalidade , Osso e Ossos/metabolismo , Osso e Ossos/patologia , Linhagem Celular Tumoral , Proliferação de Células , Quimiocina CXCL2/agonistas , Quimiocina CXCL2/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática , Masculino , MicroRNAs/agonistas , MicroRNAs/antagonistas & inibidores , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Oligorribonucleotídeos/genética , Oligorribonucleotídeos/metabolismo , Osteossarcoma/diagnóstico , Osteossarcoma/metabolismo , Osteossarcoma/mortalidade , Fenótipo , Plasmídeos/química , Plasmídeos/metabolismo , Prognóstico , Transdução de Sinais , Análise de SobrevidaRESUMO
Asthma is an inflammatory syndrome characterized by airway hyperresponsiveness, bronchial inflammation, and airway remodeling. The hypertrophy and hyperplasia of airway smooth muscle cells (ASMCs) are hallmarks of bronchial remodeling in asthma. In this study, the regulatory effects of microRNA-620 (miR-620) on ASMC proliferation and apoptosis in response to transforming growth factor ß1 (TGF-ß1) stimulation was investigated. The expression of miR-620 was significantly upregulated in TGF-ß1-treated ASMCs compared with vehicle-treated cells. Downregulation of miR-620 suppressed the proliferation and increased apoptosis in TGF-ß1-stimulated ASMCs. Phosphatase and tensin homolog (PTEN) was predicted and confirmed as a downstream target of miR-620. PTEN was upregulated in miR-620-inhibitor transfected ASMCs, but decreased in cells delivered with miR-620 mimics. Moreover, knocking down miR-620 alone efficiently reduced the phosphorylation of protein kinase B (AKT), decreased TGF-ß1-induced proliferation and promoted apoptosis in ASMCs, whereas downregulation of PTEN in miR-620 inhibitor-transfected cells restored the activation of AKT, increased TGF-ß1-triggered proliferation, and partially inhibited ASMC apoptosis. Taken together, the present study provided evidence that miR-620 increased TGF-ß1-mediated proliferation and suppressed apoptosis in ASMCs via the regulation of PTEN and AKT expression. These findings suggest that miR-620/PTEN/AKT axis may be considered as a therapeutic target for asthma treatment.
Assuntos
MicroRNAs/genética , Miócitos de Músculo Liso/efeitos dos fármacos , PTEN Fosfo-Hidrolase/genética , Proteínas Proto-Oncogênicas c-akt/genética , Fator de Crescimento Transformador beta1/farmacologia , Antagomirs/genética , Antagomirs/metabolismo , Apoptose/efeitos dos fármacos , Apoptose/genética , Pareamento de Bases , Sequência de Bases , Brônquios/citologia , Brônquios/metabolismo , Proliferação de Células/efeitos dos fármacos , Regulação da Expressão Gênica , Humanos , MicroRNAs/agonistas , MicroRNAs/antagonistas & inibidores , MicroRNAs/metabolismo , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/metabolismo , Oligorribonucleotídeos/genética , Oligorribonucleotídeos/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Cultura Primária de Células , Proteínas Proto-Oncogênicas c-akt/metabolismo , Pteridinas/farmacologia , Transdução de Sinais , Fator de Crescimento Transformador beta1/antagonistas & inibidores , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismoRESUMO
Oxaliplatin (L-OHP) is one of the effective chemotherapeutic drugs for colorectal cancer (CRC). Further investigation into the molecular mechanism of chemoresistance could improve outcomes for patients with colorectal cancer. Recently, microRNAs have been reported as a key in drug resistance of tumors. In this study, we aimed to investigate the effects of miR-153-5p in L-OHP-resistant CRC cells, and its underlying mechanism. Downregulation of miR-153-5p was observed in CRC cells, while upregulation of miR-153-5p enhances the chemosensitivity of CRC/L-OHP cells. The autophagy of CRC/L-OHP cells was markedly increased after exposure to L-OHP but abolished by the upregulation of miR-153-5p. Dual-luciferase reporter assays validated that Bcl-2 was a direct target of miR-153-5p. In conclusion, our data suggested that miR-153-5p was a mediator of cisplatin resistance in colorectal cancer by affecting Bcl-2-mediated autophagy, indicating a new therapeutic target for CRC treatment.
Assuntos
Antineoplásicos/farmacologia , Autofagia/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , MicroRNAs/genética , Oxaliplatina/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Antagomirs/genética , Antagomirs/metabolismo , Autofagia/genética , Pareamento de Bases , Sequência de Bases , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Células HCT116 , Humanos , MicroRNAs/agonistas , MicroRNAs/antagonistas & inibidores , MicroRNAs/metabolismo , Oligorribonucleotídeos/genética , Oligorribonucleotídeos/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transdução de SinaisRESUMO
Although the B-cell translocation gene 1 (BTG1) plays an important role in apoptosis and negatively regulates cell proliferation, BTG1 expression in skin squamous cell carcinoma (SCC) has not been reported. In this study, we wanted to investigate the significance of BTG1 expression in SCC and adjacent tissues. The expression of BTG1 protein and mRNA in SCC tissues and adjacent tissues were detected by immunohistochemistry technique (IHC), Western blot and reverse transcriptase-polymerase chain reaction (RT-PCR). IHC staining showed that the positive expression rate of BTG1 protein in SCC tissues was 54.00%; and the positive rate was 90.50% in the adjacent tissues. Western blot showed that the expression of BTG1 protein in SCC tissues was significantly lower than that in the adjacent tissues (P less than 0.05). RT-PCR showed that the positive rate of BTG1 mRNA in SCC was 50.50%, which was significantly lower than that in adjacent tissues 89.00% (P less than 0.05). Both BTG1 mRNA and protein expression are related to tumor diameter, stage, tumor metastasis and the degree of tumor differentiation in SCC. Patients exhibiting lower BTG1 protein expression in the SCC tissues had a significantly shorter disease-specific survival rate. BTG1 protein expression, tumor diameter, tumors site and stage were independent factors affecting the overall survival of postoperative patients. Further, BTG1 overexpression inhibited A431 cell proliferation ability, while BTG silencing enhanced A431 cell proliferation ability. The lower expression of BTG1 in SCC may be associated with the occurrence, development and prognosis of SCC.
Assuntos
Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/genética , Regulação Neoplásica da Expressão Gênica , Proteínas de Neoplasias/genética , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose/genética , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Proteínas de Neoplasias/agonistas , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/metabolismo , Estadiamento de Neoplasias , Oligorribonucleotídeos/genética , Oligorribonucleotídeos/metabolismo , Prognóstico , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Análise de SobrevidaRESUMO
The ubiquitin conjugating enzyme E2 N (UBE2N) has been reported to be involved in the tumorigenesis of several tumors, but its function in cervical carcinoma has not been investigated yet. In the present study, UBE2N was found elevated in cervical carcinoma, and patients with high UBE2N had a shorter overall survival than patients with low expression. Additionally, knockdown of UBE2N decreased the activation of MEK1/2 and p38 in cervical carcinoma cells, and UBE2N knockdown also markedly inhibited cervical carcinoma cell growth. Our further studies found that microRNA-590-3p (miR-590-3p) was significantly decreased in cervical carcinoma, and patients with high miR-590-3p had a longer overall survival than patients with low expression. Moreover, miR-590-3p expression was found negatively correlated with UBE2N expression in cervical carcinoma, and our further studies showed that miR-590-3p targeted UBE2N and inhibited its expression in cervical carcinoma. Overexpression of miR-590-3p could inhibit cervical carcinoma cell growth, but enhanced UBE2N could rescue miR-590-3p-induced cell growth inhibition in cervical carcinoma. This study indicated that targeting miR-590-3p/UBE2N axis could be a potential strategy for the treatment of cervical carcinoma.