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1.
Bioengineered ; 13(2): 2889-2901, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35040749

RESUMO

Cholangiocarcinoma (CHOL) is often diagnosed at an advanced stage; therefore, exploring its key regulatory factors is important for earlier diagnosis and treatment. This study aimed to identify the mechanisms of long non-coding RNA (lncRNA) TMPO Antisense RNA 1 (TMPO-AS1), microRNA let-7 g-5p, and high-mobility group A1 (HMGA1) proteins in CHOL. Our results, through quantitative real-time PCR and Western blot detection, showed that TMPO-AS1 and HMGA1 were overexpressed while let-7 g-5p was underexpressed in CHOL. Cell function experiments in CHOL cells revealed that TMPO-AS1 knockdown inhibited cell proliferation, colony formation, and cell migration, but induced apoptosis. TMPO-AS1 knockdown also suppressed tumor growth in vivo. Together with luciferase assay and Western blotting, we found that TMPO-AS1 could sponge let-7 g-5p to promote HMGA1 expression. Moreover, HMGA1 overexpression attenuated the effect of TMPO-AS1 downregulation in CHOL cells. Overall, our findings identified the oncogenic effect of TMPO-AS1 on CHOL cells, which may put forward a novel methodology for CHOL diagnosis and therapy.


Assuntos
Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/patologia , Proteína HMGA1a/genética , MicroRNAs/genética , Proteínas Nucleares/genética , Timopoietinas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Neoplasias dos Ductos Biliares/genética , Ductos Biliares Intra-Hepáticos/metabolismo , Ductos Biliares Intra-Hepáticos/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Transformação Celular Neoplásica/genética , Colangiocarcinoma/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Proteínas Nucleares/antagonistas & inibidores , RNA Antissenso/fisiologia , RNA Longo não Codificante/fisiologia , Timopoietinas/antagonistas & inibidores
2.
Phytopathology ; 112(4): 775-783, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34587815

RESUMO

Paenibacillus polymyxa is a beneficial bacterium for plant health. P. polymyxa TP3 exhibits antagonistic activity toward Botrytis cinerea and alleviates gray mold symptoms on the leaves of strawberry plants. Moreover, suppression of gray mold on the flowers and fruits of strawberry plants in field trials, including vegetative cells and endospores, was demonstrated, indicating the potential of strain TP3 as a biological control agent. To examine the anti-B. cinerea compounds produced by P. polymyxa TP3, we performed matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and fusaricidin-corresponding mass spectra were detected. Moreover, fusaricidin-related signals appeared in imaging mass spectrometry of TP3 when confronted with B. cinerea. By using liquid chromatography mass spectrometry-based molecular networking approach, we identified several fusaricidins including a new variant of mass/charge ratio 917.5455 with serine in the first position of the hexapeptide. Via advanced mass spectrometry and network analysis, fusaricidin-type compounds produced by P. polymyxa TP3 were efficiently disclosed and were presumed to play roles in the antagonism against gray mold pathogen B. cinerea.


Assuntos
Fragaria , Paenibacillus polymyxa , Botrytis , Fragaria/microbiologia , Paenibacillus polymyxa/genética , Fragmentos de Peptídeos , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Timopoietinas
3.
J Gastroenterol Hepatol ; 37(1): 144-153, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34370878

RESUMO

BACKGROUND AND AIM: Colorectal cancer, as a common malignant carcinoma in the gastrointestinal tract, has a high mortality globally. However, the specific molecular mechanisms of long non-coding RNA (lncRNA) thymopoietin antisense transcript 1 (TMPO-AS1) in colorectal cancer were unclear. METHODS: We tested the expression level of TMPO-AS1 via qRT-PCR in colorectal cancer cells, while the protein levels of branched chain amino acid transaminase 1 (BCAT1) and the stemness-related proteins were evaluated by western blot analysis. Colony formation, EdU staining, TUNEL, flow cytometry, and sphere formation assays were to assess the biological behaviors of colorectal cancer cells. Then, luciferase reporter, RIP, and RNA pull down assay were applied for confirming the combination between microRNA-98-5p (miR-98-5p) and TMPO-AS1/BCAT1. RESULTS: TMPO-AS1 was aberrantly expressed at high levels in colorectal cancer cells. Silenced TMPO-AS1 restrained cell proliferation and stemness and promoted apoptosis oppositely, while overexpressing TMPO-AS1 exerted the adverse effects. Furthermore, miR-98-5p was proven to a target of TMPO-AS1 inhibit cell progression in colorectal cancer. Additionally, BCAT1 was proved to enhance cell progression as the target of miR-98-5p, and it offset the effect of silenced TMPO-AS1 on colorectal cancer cells. CONCLUSION: TMPO-AS1 promotes the progression of colorectal cancer cells via sponging miR-98-5p to upregulate BCAT1 expression.


Assuntos
Neoplasias Colorretais , Proteínas Nucleares , RNA Longo não Codificante , Timopoietinas , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Timopoietinas/genética , Timopoietinas/metabolismo , Transaminases/metabolismo
4.
J Dairy Sci ; 104(12): 12925-12938, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34593235

RESUMO

Epicatechin (EC) has significant antiinflammation, antioxidation, and anticancer activities. It also provides a new alternative treatment for mastitis, which can result in great economic losses in the dairy industry if left untreated. The purpose of this study was to investigate the anti-inflammatory effects of EC on mastitis and the underlying mechanism using in vivo and in vitro systems. The use of ELISA and immunohistochemistry assays showed that EC treatment at 1.5, 7.5, 15, and 30 mg/mL decreased protein expression of inflammatory mediators, including cyclooxygenase-2 and inducible nitric oxide synthase; inflammatory cytokines, which were composed of IL-1ß, TNF-α, and IL-6 in lipopolysaccharide (LPS)-stimulated bovine mammary epithelial cell line (MAC-T); and mouse mammary gland, together with reduced filtration of T lymphocytes in the mouse mammary gland. Furthermore, EC treatment reduced LPS-induced phosphorylation levels of p65 and inhibitor of NF-κB, and blocked nuclear translocation of p65 as revealed by western blot and immunofluorescence test in MAC-T cells and the mouse mammary gland. Epicatechin also attenuated LPS-induced phosphorylation levels of mitogen-activated protein kinase members (i.e., p38, c-Jun N-terminal kinase 1/2 and extracellular regulated protein kinases 1/2). Using RNA-seq and tandem mass tag analyses, upregulation of TMEM35A and TMPO proteins was disclosed in MAC-T cells cotreated with LPS and EC. Although clustered regularly interspaced short palindromic repeats/Cas9-based knockdown of TMEM35A and TMPO attenuated abundance of phosphorylated (p)-p65, p-p38, TNF-α, and iNOS, overexpression of TMEM35A reversed EC-mediated effects in TMPO knockdown cells. Moreover, interaction between TMEM35A and TMPO was detected using the co-immunoprecipitation method. In conclusion, our data demonstrated that EC inhibited LPS-induced inflammatory response in MAC-T cells and the mouse mammary gland. Importantly, TMEM35A mediated the transmembrane transport of EC, and the interaction between TMEM35A and TMPO inhibited MAPK and NF-κB pathways.


Assuntos
Catequina , Doenças dos Bovinos , Proteínas de Membrana , Doenças dos Roedores , Timopoietinas , Animais , Anti-Inflamatórios/uso terapêutico , Catequina/farmacologia , Bovinos , Óxidos N-Cíclicos , Células Epiteliais/metabolismo , Feminino , Inflamação/tratamento farmacológico , Inflamação/veterinária , Lipopolissacarídeos , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Timopoietinas/genética , Timopoietinas/metabolismo
5.
DNA Cell Biol ; 40(7): 848-857, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34096793

RESUMO

Long noncoding RNAs (lncRNAs) play essential roles in the occurrence and development of multiple human cancers. An accumulating body of researches have investigated thymopoietin antisense RNA 1 (TMPO-AS1) as a newly discovered lncRNA, which functions as an oncogenic lncRNA that is upregulated in various human malignancies and associated with poor prognosis. Many studies have detected abnormally high expression levels of TMPO-AS1 in multiple cancers, such as lung cancer, breast cancer, colorectal cancer (CRC), hepatocellular carcinoma, CRC, gastric cancer, ovarian cancer, thyroid cancer, esophageal cancer, Wilms tumor, cervical cancer, retinoblastoma, bladder cancer, osteosarcoma, and prostate cancer. TMPO-AS1 has been subsequently demonstrated to play a pivotal role in tumorigenesis and progression. The aberrantly expressed TMPO-AS1 acts as a competing endogenous RNA (ceRNA) that inhibits miRNA expression, thus activating the expression of downstream oncogenes. This study comprehensively summarizes the aberrant expressions of TMPO-AS1 as reported in the current literature and explains the relevant biological regulation mechanisms in carcinogenesis and tumor progression. Corresponding studies have indicated that TMPO-AS1 has a potential value as a promising biomarker or a target for cancer therapy.


Assuntos
Neoplasias/genética , Proteínas Nucleares/genética , RNA Antissenso/genética , Timopoietinas/genética , Biomarcadores Tumorais/genética , Carcinogênese/genética , Proliferação de Células/genética , Progressão da Doença , Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , MicroRNAs/genética , Proteínas Nucleares/metabolismo , RNA Longo não Codificante/genética , Timopoietinas/metabolismo
6.
J Gastroenterol Hepatol ; 36(7): 1877-1888, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33295056

RESUMO

BACKGROUND AND AIM: Gastric cancer (GC) is an aggressive tumor featured by uncontrolled cell proliferation and metastasis. In recent years, long noncoding RNAs (lncRNAs) act as crucial regulators and biological markers in multiple cancers. LncRNA TMPO-AS1 has been revealed to be an oncogene in some cancers. Nevertheless, there is little known about the biological role of TMPO-AS1 in GC. METHODS: Reverse transcription-quantitative polymerase chain reaction analysis was used to examine the expression level of TMPO-AS1 in GC tissues and cells. Cell Counting Kit-8, colony formation, wound healing assays, and western blot analysis were performed to determine the role of TMPO-AS1 in GC cells. RNA pull-down, luciferase reporter, and RNA immunoprecipitation assays were used to test the interaction among TMPO-AS1, miR-126-5p, and BRCC3. RESULTS: TMPO-AS1 was highly expressed in GC tissues and cells. Upregulated TMPO-AS1 was closely associated with adverse prognosis of GC patients. Functional assays showed that TMPO-AS1 promoted GC cell proliferation, migration, and angiogenesis. Furthermore, it was found that TMPO-AS1 acted as a competing endogenous RNA for miR-126-5p to upregulate BRCC3 expression. Rescue assays revealed that TMPO-AS1 facilitated cellular progression of GC by sponging miR-126-5p and upregulating BRCC3. In addition, we found that the effects of the TMPO-AS1/miR-126-5p/BRCC3 axis on GC cell progression were related to the PI3K/Akt/mTOR pathway. CONCLUSIONS: Our study demonstrated that the TMPO-AS1/miR-126-5p/BRCC3 axis was involved in GC progression via the regulation of PI3K/Akt/mTOR pathway, which might provide a potential therapeutic strategy for GC.


Assuntos
MicroRNAs , RNA Longo não Codificante , Neoplasias Gástricas , Linhagem Celular Tumoral , Proliferação de Células/genética , Óxidos N-Cíclicos , Enzimas Desubiquitinantes , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , Neovascularização Patológica/genética , Proteínas Nucleares , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , RNA Longo não Codificante/genética , Neoplasias Gástricas/genética , Serina-Treonina Quinases TOR/genética , Timopoietinas
7.
Am J Med Sci ; 360(6): 711-720, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32988599

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC), featuring uncontrolled proliferation and migration of tumor cells, is one of the most serious malignancies with high morality. An increasing number of evidences have demonstrated that long noncoding RNAs (lncRNAs) are involved in the progression of multiple cancers. It has been acknowledged that lncRNA TMPO-AS1 plays an oncogenic role in diverse cancers. METHODS: Reverse transcription­quantitative polymerase chain reaction (RT-qPCR) was used to determine the expression of TMPO-AS1, miR-429 and GOT1 in HCC tissues and cell lines. Cell viability, proliferation, apoptosis, and stemness characteristics were detected by Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry, sphere formation and western blot assays, separately. The relationship among TMPO-AS1, miR-429 and GOT1 was predicted by starBase database and confirmed using luciferase reporter and RNA pull-down assays. RESULTS: In this study, our findings revealed that TMPO-AS1 expression was upregulated in HCC tissues and cell lines. TMPO-AS1 aggravated HCC progression via promoting cell proliferation, stemness as well as suppressing cell apoptosis. Further, molecular mechanism exploration discovered that TMPO-AS1 functioned as a molecular sponge for miR-429 and GOT1 served as a downstream target gene of miR-429 in HCC. Furthermore, there was a negative relationship between GOT1 and miR-429 as well as a positive correlation between GOT1 and TMPO-AS1 in HCC. Rescue assays suggested that overexpression of GOT1 partially reversed the inhibitory effects of TMPO-AS1 knockdown on HCC progression. CONCLUSIONS: Taken together, these findings indicated that TMPO-AS1 acted as a tumor motivator to expedite HCC progression via targeting miR-429/GOT1 axis, which may provide a fresh treatment strategy for HCC.


Assuntos
Aspartato Aminotransferase Citoplasmática/metabolismo , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , MicroRNAs/metabolismo , Proteínas Nucleares/metabolismo , RNA Longo não Codificante/metabolismo , Timopoietinas/metabolismo , Humanos
8.
Eur Rev Med Pharmacol Sci ; 24(17): 8740-8746, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32964962

RESUMO

OBJECTIVE: This study aims to uncover the in vitro influences of lncRNA TMPO-AS1 on the progression of bladder cancer (BLCA) and the underlying mechanism. PATIENTS AND METHODS: Expression levels of TMPO-AS1 in BLCA tissues and normal bladder tissues were analyzed in The Cancer Genome Atlas (TCGA) database. Differential expressions of TMPO-AS1 in BLCA tissues and normal bladder epithelial tissues were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Potential influence of TMPO-AS1 on prognosis of BLCA patients was assessed. In vitro influences of TMPO-AS1 on proliferative and migratory abilities in T24 and UMUC-3 cells were evaluated by Cell Counting Kit-8 (CCK-8), transwell, and wound healing assay, respectively. Finally, the correlation between TMPO-AS1 and its sense RNA TMPO was assessed by analyzing TCGA database, clinical samples, and BLCA cell lines. RESULTS: By analyzing TCGA database and clinical samples, it was found that TMPO-AS1 was upregulated in BLCA tissues compared with that in normal bladder tissues. Worse survival was observed in BLCA patients with high expression of TMPO-AS1. TMPO-AS1 level was correlated to muscle invasiveness and TNM stage of BLCA patients. In T24 and UMUC-3 cells, the knockdown of TMPO-AS1 suppressed proliferative and migratory abilities. TMPO-AS1 level was positively correlated to that of its sense RNA TMPO. Moreover, the knockdown of TMPO-AS1 downregulated mRNA and protein levels of TMPO in BLCA cells. CONCLUSIONS: TMPO-AS1 is upregulated in BLCA tissue and closely linked to poor prognosis of BLCA patients.


Assuntos
Proteínas Nucleares/genética , RNA Longo não Codificante , Timopoietinas/genética , Neoplasias da Bexiga Urinária/genética , Linhagem Celular , Movimento Celular/genética , Proliferação de Células/genética , Epitélio/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/metabolismo , Prognóstico , Timopoietinas/metabolismo , Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia
9.
Rev Assoc Med Bras (1992) ; 66(6): 784-788, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32696866

RESUMO

OBJECTIVE Long noncoding RNA (lncRNAs) are frequently abnormally expressed in tumors and involved in the occurrence and progression of human cancer. Recently, a disease-related lncRNA, TMPO antisense RNA 1 (TMPO-AS1), was identified to be dysregulated in several tumors. Hence, we aimed to demonstrate whether TMPO-AS1 could be a promising prognostic marker for patients with laryngeal squamous cell carcinoma (LSCC). METHODS RT-PCR was performed to test TMPO-AS1 expressions in 187 LSCC specimens compared with matched normal specimens. Chi-squared tests were used to determine the associations between TMPO-AS1 expressions and the clinicopathological characteristics of LSCC patients. Then, the clinical outcome of LSCC patients who had lower or higher TMPO-AS1 expression was analyzed using Kaplan-Meier assays. Finally, a Cox proportional hazards model was carried out to evaluate the prognostic values of TMPO-AS1 and other clinical features. RESULTS We found that TMPO-AS1 was distinctly upregulated in human LSCC tissues compared with corresponding normal specimens (p < 0.01). Higher expressions of TMPO-AS1 were observed to be positively associated with the clinical stage (p = 0.020) and lymph node metastasis (p = 0.027). A clinical study in 187 patients revealed that patients with TMPO-AS1 low expressions had poorer survival than those with TMPO-AS1 high expressions (p = 0.0012). In addition, the result of multivariate assays demonstrated TMPO-AS1 expression is an independent predictor for the overall survival of LSCC patients. CONCLUSIONS TMPO-AS1 might be considered a novel molecule involved in LSCC progression, which provides a possible prognostic biomarker.


Assuntos
Carcinoma de Células Escamosas/diagnóstico , Neoplasias Laríngeas/diagnóstico , Timopoietinas/metabolismo , Óxidos N-Cíclicos , Humanos , Prognóstico , RNA Longo não Codificante
10.
Rev. Assoc. Med. Bras. (1992) ; 66(6): 784-788, June 2020. tab, graf
Artigo em Inglês | Sec. Est. Saúde SP, LILACS, Sec. Est. Saúde SP | ID: biblio-1136281

RESUMO

SUMMARY OBJECTIVE Long noncoding RNA (lncRNAs) are frequently abnormally expressed in tumors and involved in the occurrence and progression of human cancer. Recently, a disease-related lncRNA, TMPO antisense RNA 1 (TMPO-AS1), was identified to be dysregulated in several tumors. Hence, we aimed to demonstrate whether TMPO-AS1 could be a promising prognostic marker for patients with laryngeal squamous cell carcinoma (LSCC). METHODS RT-PCR was performed to test TMPO-AS1 expressions in 187 LSCC specimens compared with matched normal specimens. Chi-squared tests were used to determine the associations between TMPO-AS1 expressions and the clinicopathological characteristics of LSCC patients. Then, the clinical outcome of LSCC patients who had lower or higher TMPO-AS1 expression was analyzed using Kaplan-Meier assays. Finally, a Cox proportional hazards model was carried out to evaluate the prognostic values of TMPO-AS1 and other clinical features. RESULTS We found that TMPO-AS1 was distinctly upregulated in human LSCC tissues compared with corresponding normal specimens (p < 0.01). Higher expressions of TMPO-AS1 were observed to be positively associated with the clinical stage (p = 0.020) and lymph node metastasis (p = 0.027). A clinical study in 187 patients revealed that patients with TMPO-AS1 low expressions had poorer survival than those with TMPO-AS1 high expressions (p = 0.0012). In addition, the result of multivariate assays demonstrated TMPO-AS1 expression is an independent predictor for the overall survival of LSCC patients. CONCLUSIONS TMPO-AS1 might be considered a novel molecule involved in LSCC progression, which provides a possible prognostic biomarker.


RESUMO OBJETIVO RNAs longos não-codificantes (INcRNAs) são frequentemente expressos anormalmente em tumores e estão envolvidos na ocorrência e progressão do câncer humano. Recentemente, um INcRNA relacionado com a doença, o TMPO antisense RNA 1 (TMPO-AS1), foi identificado como desregulado em vários tumores. Por isso, procuramos demonstrar se o TMPO-AS1 poderia ser um marcador de prognóstico promissor para pacientes com carcinoma de células escamosas da laringe (LSCC). MÉTODOS RT-PCR foi realizado para medir as expressões do TMPO-AS1 em 187 espécimes de LSCC em comparação com espécimes normais correspondentes. Foram utilizados testes Qui-quadrado para determinar as associações entre as expressões do TMPO-AS1 e as características clínicas dos pacientes com LSCC. Em seguida, o desfecho clínico dos pacientes com LSCC que tinham uma expressão do TMPO-AS1 inferior ou superior foi analisado com ensaios Kaplan-Meier. Por último, o modelo de riscos proporcionais de Cox foi utilizado para avaliar o valor prognóstico do TMPO-AS1 e outras características clínicas. RESULTADOS Observamos que o TMPO-AS1 estava claramente super-regulado nos tecidos de LSCC humanos em comparação com os espécimes normais correspondentes (p<0,01). Expressões mais elevadas de TMPO-AS1 estavam positivamente associadas ao estágio clínico (p=0,020) e à metástase linfática (p=0,027). Um estudo clínico com 187 pacientes revelou que aqueles com expressões mais baixas de TMPO-AS1 tiveram uma sobrevida pior do que aqueles com expressões elevadas de TMPO-AS1 (p=0,0012). Além disso, o resultado de ensaios multivariados demonstrou que a expressão do TMPO-AS1 é um preditor independente para a sobrevida global de pacientes com LSCC. CONCLUSÕES TMPO-AS1 pode ser considerado uma molécula nova envolvida na progressão do LSCC, o que proporciona um possível biomarcador de prognóstico.


Assuntos
Humanos , Timopoietinas/metabolismo , Carcinoma de Células Escamosas/diagnóstico , Neoplasias Laríngeas/diagnóstico , Prognóstico , Óxidos N-Cíclicos , RNA Longo não Codificante
11.
Pathol Res Pract ; 216(4): 152853, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32139259

RESUMO

BACKGROUND: Long non-coding RNA (lncRNA) TMPO antisense RNA 1 (TMPO-AS1) is reported to be oncogenic in prostate cancer and lung cancer. This study aims to investigate the expression and biological function of it in retinoblastoma (RB), and explore its regulatory role for miR-199a-5p and hypoxia-inducible factor-1α (HIF-1α). METHODS: Paired RB samples were collected, and the expression levels of TMPO-AS1, miR-199a-5p and HIF-1α were examined by quantitative real-time polymerase chain reaction (qRT-PCR); TMPO-AS1 overexpressing plasmids and TMPO-AS1 shRNA were transfected into HXO-RB44 and SO-Rb50 cell lines respectively, and then proliferation, migration and invasion of RB cells were detected by CCK-8 assay and Transwell method. qRT-PCR and western blot were used to analyze the regulatory function of TMPO-AS1 on miR-199a-5p and HIF-1α; luciferase reporter gene assay was used to determine the regulatory relationship between miR-199a-5p and TMPO-AS1. RESULTS: TMPO-AS1 was significantly up-regulated in cancerous tissues of RB samples (relatively expression: 2.97 vs 3.93, p < 0.001), negatively correlated with miR-199a-5p (r=-0.4813, p < 0.01). There was one binding site on TMPO-AS1 for miR-199a-5p. After transfection of TMPO-AS1 shRNAs into RB cells, the proliferation, migration and invasion of cancer cells was significantly inhibited, while TMPO-AS1 had opposite effects; TMPO-AS1 was also demonstrated to regulate the expression of HIF-1α on both mRNA and protein levels via negatively regulating miR-199a-5p. CONCLUSION: TMPO-AS1 is abnormally up-regulated in RB tissues, and it can modulate the proliferation and migration of RB cells. It has the potential to be the "ceRNA" to regulate HIF-1α expression by sponging miR-199a-5p.


Assuntos
Regulação Neoplásica da Expressão Gênica/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/biossíntese , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Neoplasias da Retina/patologia , Retinoblastoma/patologia , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Proteínas Nucleares/metabolismo , Fenótipo , RNA Antissenso/metabolismo , Neoplasias da Retina/genética , Neoplasias da Retina/metabolismo , Retinoblastoma/genética , Retinoblastoma/metabolismo , Timopoietinas/metabolismo , Regulação para Cima
12.
Int J Biochem Cell Biol ; 122: 105702, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32087328

RESUMO

As reported in numerous studies, long non-coding RNAs (lncRNAs) exert significant effect on the regulation of tumor development. LncRNA TMPO antisense RNA 1 (TMPO-AS1) has been confirmed to be implicated in the development of several cancers. However, its clinical significance is still largely unknown in bladder cancer (BCa). In this study, high expression of TMPO-AS1 was revealed in BCa tissues and cell lines, and TMPO-AS1 predicted poor prognosis. Moreover, TMPO-AS1 facilitated cell growth. Additionally, TMPO-AS1 also boosted the migration and invasion of BCa cells. Mechanistically, overexpressed EBF transcription factor 1 (EBF1) in BCa cell was verified to promote the transcription of TMPO-AS1. Later, we found that TMPO-AS1 was a cytoplasmic RNA and could sponge miR-98-5p. Besides, it was validated that EBF1 is a target gene of miR-98-5p and negatively correlated with miR-98-5p in terms of expression level. According to the results of rescue experiments, we observed that EBF1 overexpression restored the repressive effect of TMPO-AS1 silencing on BCa development. Our research is the first to disclose the biological role and molecular mechanism of TMPO-AS1 in BCa, and TMPO-AS1 might be identified as a new therapeutic target for BCa patients.


Assuntos
MicroRNAs/metabolismo , Proteínas Nucleares/genética , RNA Antissenso/metabolismo , Timopoietinas/genética , Transativadores/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Processos de Crescimento Celular/fisiologia , Linhagem Celular , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Progressão da Doença , Retroalimentação Fisiológica , Feminino , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , RNA Antissenso/biossíntese , Transdução de Sinais , Transativadores/genética , Transfecção , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia
13.
Biomed Pharmacother ; 125: 109989, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32062549

RESUMO

Long noncoding RNAs (lncRNAs) play critical roles in the pathogenesis of various diseases, including a variety of tumors. Nevertheless, its functional roles and underlying molecular basis for their dysregulation in lung adenocarcinoma (LUAD) are largely unknown. Herein, in our study, we identified that lncRNA TMPO-AS1 is significantly upregulated in LUAD tissues and cell lines. Knockdown of TMPO-AS1 remarkably suppressed LUAD cell growth, induced apoptosis as well as G1/S arrest, and inhibited LUAD cell invasion, whereas overexpression of TMPO-AS1 exerts the opposite effects. Next, we implemented online database analysis tools to find that mir-383-5p could target TMPO-AS1, and our data showed that TMPO-AS1 was negatively correlated with mir-383-5p in LUAD specimens. We found that inhibiting miR-383-5p expression led to a marked upregulation of TMPO-AS1 level, while overexpression of miR-383-5p markedly suppressed TMPO-AS1's expression and function, suggesting that TMPO-AS1 is negatively regulated by miR-383-5p. In addition, we confirmed that miR-383-5p directly targeted TMPO-AS1 by binding to microRNA binding sites in the TMPO-AS1 sequence with a luciferase reporter and RIP assays. Besides, the inhibition of TMPO-AS1 significantly suppressed the tumorigenesis ability of LUAD cells in vivo. Together, these results demonstrate that TMPO-AS1 could be considered as a potential therapeutic target for LUAD patients.


Assuntos
Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Proteínas Nucleares/genética , RNA Antissenso , RNA Longo não Codificante/genética , Timopoietinas/genética , Animais , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Transformação Celular Neoplásica/genética , Modelos Animais de Doenças , Progressão da Doença , Técnicas de Silenciamento de Genes , Humanos , Imuno-Histoquímica , Camundongos , Interferência de RNA
14.
J Gastrointest Cancer ; 51(3): 952-956, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31768869

RESUMO

PURPOSE: Long noncoding RNA (lncRNA) has been identified as an important modulator of gene expression and other activities of the cells. This kind of genes also has a significant role in the growth and development of human cancers, including colorectal cancer (CRC). Among lncRNAs, thymopoietin (TMPO)-antisense RNA 1 (TMPO-AS1) is of particular significance and might have a role in CRC regulation. The current study aimed to determine the involvement of TMPO-AS1 in CRC patients. METHODS: In this study, 50 pairs of tumor and tumor marginal samples of CRC patients were investigated to assess the expression level of TMPO-AS1 in this cancer. For this purpose, the total RNA was isolated from the tissues using the TRIzol RNA extraction method, and after synthesis of the complementary DNA, the TMPO-AS1 expression was measured by quantitative real-time PCR (qRT-PCR) technique. In addition, clinicopathological characteristics of the CRC patients were analyzed in the study groups. RESULTS: The findings demonstrated the overexpression of TMPO-AS1 in CRC tissues. Interestingly, the expression level of TMPO-AS1 was significantly correlated with clinicopathological features of the patients such as lymph node and distant metastasis. CONCLUSION: The overexpression of TMPO-AS1 gene in CRC suggests that this lncRNA and its underlying signaling pathways can be considered a prognostic tumor marker and may pave the way for the future development of novel therapeutic options for CRC.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica , Proteínas Nucleares/antagonistas & inibidores , RNA Antissenso/genética , RNA Longo não Codificante/genética , Timopoietinas/antagonistas & inibidores , Neoplasias Colorretais/genética , Neoplasias Colorretais/cirurgia , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida
15.
J Cell Biochem ; 121(3): 2284-2293, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31680323

RESUMO

Osteosarcoma (OS) is a common kind of aggressive tumor in bone which was mostly identified in children and adolescents with extremely high risk of death. Accumulating research works have displayed that long noncoding RNAs (lncRNAs) exert an essential role in the development of multiple cancers. It has been reported that TMPO-AS1 is an oncogene in cancers; nonetheless, its molecular mechanism in OS is totally unclear. Our present study elucidated that a remarkable overexpression of TMPO-AS1 was found in OS tissues and cells. Moreover, TMPO-AS1 depletion restrained Wnt/ß-catenin pathway and cell proliferation as well as facilitated cell apoptosis. Further molecular mechanism investigations showed that TMPO-AS1 can sponge to miR-199a-5p. Moreover, miR-199a-5p was at a low level at OS cells. Importantly, miR-199a-5p's overexpression was associated with the OS cells' decreased proliferation and increased apoptosis. In addition, WNT7B was confirmed as a downstream gene of miR-199a-5p. Also the WNT7B expression was reversely modulated by miR-199a-5p and positively modulated by TMPO-AS1. Rescue experiments suggested that downregulated WNT7B rescued miR-199a-5p inhibitor-mediated repression on OS progression, but the treatment of LiCl counteracted the effect of WNT7B downregulation. In a word, TMPO-AS1 serves as a competing endogenous RNA to boost osteosarcoma tumorigenesis by regulating miR-199a-5p/WNT7B axis, which provided an underlying therapeutic target for patients with OS.


Assuntos
Biomarcadores Tumorais/metabolismo , MicroRNAs/genética , Proteínas Nucleares/antagonistas & inibidores , Osteossarcoma/patologia , RNA Antissenso/genética , RNA Longo não Codificante/genética , Timopoietinas/antagonistas & inibidores , Proteínas Wnt/metabolismo , Apoptose , Biomarcadores Tumorais/genética , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas Nucleares/genética , Osteossarcoma/genética , Osteossarcoma/metabolismo , Prognóstico , Timopoietinas/genética , Células Tumorais Cultivadas , Proteínas Wnt/genética
16.
Mol Cell Biochem ; 464(1-2): 1-9, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31673920

RESUMO

Glioblastoma is the most common and deadly type of brain cancer. The poor prognosis may be largely attributed to inadequate disease response to current chemotherapeutic agents. Activation of p38 is associated with deleterious outcomes in glioblastoma patients, as its signaling mediates chemoresistance mechanisms. Antimicrobial peptide tilapia piscidin (TP) 4 was identified from Nile tilapia (Oreochromis niloticus) and exhibits strong bactericidal effects on Gram-positive and Gram-negative bacteria. TP4 also has anticancer activity toward human triple-negative breast cancer cells and glioblastoma cells. In the present study, we tested the cytotoxic effects of combined TP4 and p38 inhibitors on glioblastoma U251 cells. We found that the combination of TP4 and p38 inhibitors (SB202190 and VX-745) enhanced cytotoxicity in U251 glioblastoma cells but not noncancerous neural cells. Cytotoxicity from the combination treatments proceeded via necrosis and not apoptosis. Mechanistically, SB202190 potentiated TP4-induced mitochondrial dysfunction, reactive oxygen species generation and unbalanced antioxidant status, which resulted in necrotic cell death. Thus, we demonstrated for the first time that combinations of TP4 and p38 inhibitors have the potential to preferentially target glioblastoma cells, while sparing noncancerous neural cells.


Assuntos
Peptídeos Catiônicos Antimicrobianos/farmacologia , Glioblastoma/tratamento farmacológico , Imidazóis/farmacologia , Proteínas de Neoplasias/antagonistas & inibidores , Fragmentos de Peptídeos/farmacologia , Piridazinas/farmacologia , Piridinas/farmacologia , Pirimidinas/farmacologia , Timopoietinas/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Animais , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Feminino , Glioblastoma/enzimologia , Glioblastoma/patologia , Humanos , Proteínas de Neoplasias/metabolismo , Tilápia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/enzimologia , Neoplasias de Mama Triplo Negativas/patologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
17.
Zhonghua Zhong Liu Za Zhi ; 41(10): 742-747, 2019 Oct 23.
Artigo em Chinês | MEDLINE | ID: mdl-31648495

RESUMO

Objective: To investigate the effect of thymopoietin (TMPO) gene deleted by small interfering RNA (RNAi) on the proliferation and apoptosis of lung cancer cell A549 and its mechanism. Methods: TMPO siRNA was transfected into A549 cells by lipofection. The transfected siRNA control was used as a negative control, and the parent cells were used as blank control. Forty-eight hours later, the expression of TMPO in the transfected cells was detected by real-time fluorescent quantitative polymerase chain reaction (RT-PCR) and Western blot. Cell proliferation was detected by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) assay, cell cycle and apoptosis were detected by flow cytometry, the protein levels of proliferating cell nuclear antigen (PCNA), cleaved caspase-3, notch receptor 1 (Notch1) and mammalian rapamycin target protein (mTOR) were detected by Western blot analysis. Results: The results of RT-PCR and Western blot showed that the expression levels of TMPO mRNA in the blank control group, the negative control group and TMPO siRNA transfected group were (1.01±0.11), (0.99±0.10), (0.36±0.04), respectively, the protein levels were (0.27±0.02), (0.29±0.03), (0.08±0.10), respectively. The expression levels of TMPO mRNA and protein in the transfected group were significantly lower than those in the blank control and negative control group (P<0.05). The results of MTT assay showed that the OD values of the blank control group, the negative control group and the transfected group were (0.35±0.04), (0.37±0.04) and (0.34±0.03) at 24 h of transfection, respectively. The OD values at 48 h were (0.47±0.06), (0.46±0.08), (0.37±0.04), the OD values at 72 h were (0.75±0.08), (0.73±0.07), (0.49±0.05), respectively, and the OD values at 96 h were (1.09±0.07), (1.06±0.08), (0.56±0.06). The proliferation abilities of the transfected cells at 48, 72, 96 h were significantly lower than those of the blank control and the negative control group (P<0.05). The results of flow cytometry showed that the proportion of G(0)/G(1) phase cells in blank control group, negative control group and transfection group were (62.55±2.03)%, (61.24±3.15)%, (47.35±2.44)%, respectively. The proportion of cells in S phase were (17.12±1.31)%, (17.70±2.01)%, and (20.81±2.06)%, respectively. The proportion of cells in G(2)/M phase were (20.33±1.43)%, (21.06±1.52)%, (31.84±2.76)%, respectively. The proportion of cells in G(0)/G(1) phase of transfection group was significantly lower than those of blank control and negative control group (P<0.05). The proportion of cells in G(2)/M phase of transfection group was significantly higher than those of blank control and negative control group (P<0.05). The apoptosis ratio of the transfection group was (34.10±2.69)%, significantly higher than (2.96±0.03)% of the blank control and (3.01±0.04)% of the negative control group (P<0.05). Western blot analysis showed that PCNA, Notch1 and mTOR proteins were down-regulated while cleaved caspase-3 protein was up-regulated in A549 cells after deletion of TMPO. Conclusion: The inhibition of TMPO gene expression induced by small interfering RNA can significantly inhibit the proliferation and induce apoptosis of A549 cells, and the mechanism is associated with the inhibition of the activation of Notch1/mTOR signaling pathway.


Assuntos
Apoptose/fisiologia , Proliferação de Células/fisiologia , Neoplasias Pulmonares/patologia , Timopoietinas/metabolismo , Animais , Apoptose/genética , Western Blotting , Linhagem Celular Tumoral , Neoplasias Pulmonares/metabolismo , Proteínas Nucleares , RNA Interferente Pequeno , Reação em Cadeia da Polimerase em Tempo Real , Timopoietinas/genética , Transfecção
18.
Mol Cell Biol ; 39(23)2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31501276

RESUMO

Acquired endocrine therapy resistance is a significant clinical problem for breast cancer patients. In recent years, increasing attention has been paid to long noncoding RNA (lncRNA) as a critical modulator for cancer progression. Based on RNA-sequencing data of breast invasive carcinomas in The Cancer Genome Atlas database, we identified thymopoietin antisense transcript 1 (TMPO-AS1) as a functional lncRNA that significantly correlates with proliferative biomarkers. TMPO-AS1 positivity analyzed by in situ hybridization significantly correlates with poor prognosis of breast cancer patients. TMPO-AS1 expression was upregulated in endocrine therapy-resistant MCF-7 cells compared with levels in parental cells and was estrogen inducible. Gain and loss of TMPO-AS1 experiments showed that TMPO-AS1 promotes the proliferation and viability of estrogen receptor (ER)-positive breast cancer cells in vitro and in vivo Global expression analysis using a microarray demonstrated that TMPO-AS1 is closely associated with the estrogen signaling pathway. TMPO-AS1 could positively regulate estrogen receptor 1 (ESR1) mRNA expression by stabilizing ESR1 mRNA through interaction with ESR1 mRNA. Enhanced expression of ESR1 mRNA by TMPO-AS1 could play a critical role in the proliferation of ER-positive breast cancer. Our findings provide a new insight into the understanding of molecular mechanisms underlying hormone-dependent breast cancer progression and endocrine resistance.


Assuntos
Neoplasias da Mama/genética , Receptor alfa de Estrogênio/genética , Proteínas Nucleares/genética , RNA Antissenso/genética , Timopoietinas/genética , Adulto , Idoso , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Sobrevivência Celular/fisiologia , Progressão da Doença , Receptor alfa de Estrogênio/metabolismo , Feminino , Técnicas de Silenciamento de Genes , Humanos , Células MCF-7 , Pessoa de Meia-Idade , Proteínas Nucleares/metabolismo , Prognóstico , RNA Antissenso/metabolismo , RNA Longo não Codificante/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais , Timopoietinas/metabolismo , Ativação Transcricional
19.
J Gene Med ; 21(11): e3125, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31483914

RESUMO

BACKGROUND: Accumulating evidence has shown that long non-coding RNAs play a key role in cancer initiation and development. However, the effect of TMPO antisense RNA 1 (TMPO-AS1) on the progression of cervical cancer (CC) remains to be determined. METHODS: The mRNA expression of TMPO-AS1, miR-577 and RAB14 was measured by a quantitative reverse transcriptase-polymerase chain reaction. The protein level of RAB14 was detected by western blotting. The function of TMPO-AS1 in CC was measured via Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine and transwell assays, as well as by flow cytometry analysis. Nuclear-cytoplasmic fractionation and RNA-fluorescence in situ hybridization validated the subcellular position of TMPO-AS1. An interaction between miR-577 and TMPO-AS1 or RAB14 was confirmed by luciferase reporter, RNA pull-down and RNA immunoprecipitation assays. RESULTS: TMPO-AS1 was highly expressed in CC. In addition, TMPO-AS1 knockdown inhibited proliferation and migration, and also induced apoptosis. TMPO-AS1 located in the cytoplasm and promoted RAB14 expression by absorbing miR-577. RAB14 overexpression or miR-577 knockdown restored the suppressing effect of TMPO-AS1 knockdown on the biological behavior of CC cells. CONCLUSIONS: The present study has revealed a novel TMPO-AS1/miR-577/RAB14 regulatory axis in the pathogenesis of CC, highlighting TMPO-AS1 as a promising therapeutic target for CC patients.


Assuntos
Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Proteínas Nucleares/genética , Interferência de RNA , RNA Antissenso/genética , Timopoietinas/genética , Neoplasias do Colo do Útero/genética , Proteínas rab de Ligação ao GTP/genética , Linhagem Celular Tumoral , Progressão da Doença , Feminino , Inativação Gênica , Humanos , Neoplasias do Colo do Útero/patologia
20.
Biochem Biophys Res Commun ; 516(2): 486-493, 2019 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-31230752

RESUMO

Long noncoding RNAs (lncRNAs), a large group of RNAs with limited or no protein-coding capacity, have been demonstrated to play critical roles in human malignancy. The aim of this study is to examine the expression and function TMPO antisense transcript 1 (TMPO-AS1) in non-small cell lung cancer (NSCLC). Here, we found that the expression of both TMPO-AS1 and TMPO mRNA levels were overexpressed in NSCLC cells lines and tissues. A significant positive correlation was observed between TMPO-AS1 and TMPO mRNA levels. The upregulation of TMPO-AS1, TMPO mRNA and protein levels were associated with tumor progression of NSCLC. More importantly, through antisense pairing with TMPO mRNA, TMPO-AS1 regulates TMPO mRNA stability. Knockdown of TMPO-AS1 decreased the mRNA and protein levels of TMPO in NSCLC cells. An overlapping (OL) region was found between TMPO-AS1 and TMPO exon 1 and overexpression of TMPO-AS1-OL elevated the mRNA and protein levels of TMPO. Functionally, the downregulation of TMPO-AS1 significantly inhibited cells proliferation, colony formation, migration and invasiveness in vitro, and tumor growth in vivo. In contrast, overexpression of TMPO could promote the aggressive behaviors of NSCLC cells in vitro. Our findings indicate that TMPO-AS1 contributes to lung carcinogenesis, which may be partially through upregulation TMPO.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Proteínas Nucleares/genética , RNA Longo não Codificante/genética , Timopoietinas/genética , Animais , Carcinogênese/genética , Carcinogênese/patologia , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica , Proteínas Nucleares/metabolismo , Prognóstico , Modelos de Riscos Proporcionais , Estabilidade de RNA/genética , RNA Antissenso , RNA Longo não Codificante/metabolismo , Timopoietinas/metabolismo , Regulação para Cima/genética
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