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1.
Clin. transl. oncol. (Print) ; 26(3): 584-596, mar. 2024.
Artigo em Inglês | IBECS | ID: ibc-230789

RESUMO

Ovarian cancer (OC) has the highest mortality rate among female reproductive system tumours, with limited efficacy of traditional treatments and 5-year survival rates that rarely exceed 40%. Circular RNA (circRNA) is a stable endogenous circular RNA that typically regulates protein expression by binding to downstream miRNA. It has been demonstrated that circRNAs play an important role in the proliferation, migration, and glucose metabolism (such as the Warburg effect) of OC and can regulate the expression of glucose metabolism-related proteins such as GLUT1 and HK2, promoting anaerobic glycolysis of cancer cells, increasing glucose uptake and ATP production, and affecting energy supply and biosynthetic substances to support tumour growth and invasion. This review summarises the formation and characteristics of circRNAs and focuses on their role in regulating glucose metabolism in OC cells and their potential therapeutic value, providing insights for identifying new therapeutic targets (AU)


Assuntos
Humanos , Feminino , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , MicroRNAs/genética , MicroRNAs/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , /genética
2.
Clin. transl. oncol. (Print) ; 26(3): 698-708, mar. 2024.
Artigo em Inglês | IBECS | ID: ibc-230799

RESUMO

Purpose There is compelling evidence that long-stranded non-coding RNAs (lncRNAs) play an important role in the progression of hepatocellular carcinoma (HCC). The aim of this study was to investigate the role of lncRNA XXYLT1 antisense-2 (XXYLT1-AS2) in HCC progression. Methods Real-time PCR was used to assess the levels of XXYLT1-AS2 in plasma from HCC and normal patients. Cell proliferation, apoptosis, migration, and invasion were monitored, and tumor xenografts were established to investigate the biological functions of XXYLT1-AS2 by gain-of-function and loss-of-function studies in vitro and in vivo, the expression of autophagy biomarkers and transcriptional factor EB (TFEB) was examined by immunoprecipitation, ubiquitination assays, and western blotting. Autophagy inhibitor, 3-methyladenine (3MA), and proteasome inhibitor, MG132, were used to verify the role of autophagy in HCC progression and the effect of XXYLT1-AS2 on TFEB ubiquitination, respectively. Results In this study, we identified that lncRNA XXYLT1-AS2 is highly expressed in HCC plasma and promotes tumor growth in vivo. In functional studies, it was found that silent expression of XXYLT1-AS2 inhibited HCC proliferation, migration, invasion, and activated autophagy of HCC cells, which were attenuated by autophagy inhibitor, 3MA. Mechanistically, XXYLT1-AS2 decreased the protein level of TFEB through promoting its degradation by ubiquitin proteasome pathway. Conclusion XXYLT1-AS2 plays an oncogenic role in HCC progression through inhibition of autophagy via promoting the degradation of TFEB, and thus could be a novel target for HCC treatment (AU)


Assuntos
Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Autofagia/genética , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Movimento Celular
3.
Clin. transl. oncol. (Print) ; 26(2): 363-374, feb. 2024.
Artigo em Inglês | IBECS | ID: ibc-230182

RESUMO

Introduction The critical role of microRNA-128 (miR-128) in gastrointestinal-related diseases has been documented. In the current study, we tried to clarify the specific role miR-128 in gastrointestinal stromal tumor (GIST) and the underlying mechanism. Methods Differentially expressed genes in GIST were identified following bioinformatics analysis. Then, expression patterns of miR-128 and B-lymphoma Mo-MLV insertion region 1 (BMI-1) in clinical tissue samples and cell lines were characterized, followed by validation of their correlation. GIST-T1 cells were selected and transfected with different mimic, inhibitor, or siRNA plasmids, after which the biological functions were assayed. Results We identified low miR-128 and high BMI-1 expression in GIST tissues of 78 patients and 4 GIST cell lines. Ectopic expression of miR-128 or silencing of BMI-1 suppressed the malignant potentials of GIST-T1 cells. As a target of miR-128, BMI-1 re-expression could partly counteract the suppressive effect of miR-128 on the malignancy of GIST-T1 cells. Conclusion Our study provided evidence that miR-128-mediated silencing of BMI-1 could prevent malignant progression of GIST, highlighting a promising anti-tumor target for combating GIST (AU)


Assuntos
Humanos , Tumores do Estroma Gastrointestinal/genética , Tumores do Estroma Gastrointestinal/patologia , Linfoma , MicroRNAs/genética , MicroRNAs/metabolismo , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , RNA Interferente Pequeno/farmacologia
4.
Clin. transl. oncol. (Print) ; 26(2): 398-413, feb. 2024.
Artigo em Inglês | IBECS | ID: ibc-230185

RESUMO

Introduction ABL2 contributes to the oncogenic potential of cancers, pointing to its inhibition as a possible strategy against malignant diseases. Bioinformatics prediction of upstream effector miR-30a-5p for ABL2 allowed us to hypothesize and then validate mechanistic actions of miR-30a-5p in lung adenocarcinoma (LUAD). Materials and methods The ABL2 expression in LUAD was analyzed in the TCGA data, clinical samples, and cell lines. The shRNA-mediated silencing of ABL2 was introduced to illustrate its effect on malignant phenotypes of LUAD cells. The binding affinity between ABL2 and miR-30a-5p was verified by luciferase activity and RNA pull-down assay. Ectopic expression, knockdown methods, and PI3K inhibitor LY294002 were used to investigate their effects on in vitro biological characteristics and in vivo tumor growth of LUAD cells. Using nude mouse lung adenocarcinoma in situ and brain metastasis models to validate the inhibitory effect of miR-30a-5p on LUAD by regulating the ABL2/PI3K/AKT signaling axis. Results High expression of ABL2 and poor expression of miR-30a-5p were noticed in LUAD tissues and cell lines. Importantly, miR-30a-5p was demonstrated to target and downregulate ABL2, subsequently inactivating the PI3K/AKT pathway. miR-30a-5p inhibited the malignant phenotypes of LUAD cells by inhibiting ABL2 expression and inactivating the PI3K/AKT pathway. For in vivo experiments, miR-30a-5p was substantiated to thwart tumor tumorigenesis by regulating the ABL2/PI3K/AKT axis. In addition, miR-30a-5p suppresses the occurrence and development of in situ lung cancer and brain metastasis via the ABL2/PI3K/AKT signaling pathway. Conclusion This study underscores the inhibitory role of miR-30a-5p in LUAD through the ABL2/PI3K/AKT axis, which may be a viable target for LUAD treatment (AU)


Assuntos
Animais , Camundongos , Adenocarcinoma de Pulmão/genética , Neoplasias Encefálicas , Carcinoma de Mama in situ , Neoplasias Pulmonares , MicroRNAs/genética , Camundongos Nus , Proteínas Proto-Oncogênicas c-akt
5.
Clin. transl. oncol. (Print) ; 26(2): 414-423, feb. 2024.
Artigo em Inglês | IBECS | ID: ibc-230186

RESUMO

Background Cholangiocarcinoma (CCA) is a heterogeneous malignancy. The aim of the study was to investigate the regulatory role of long noncoding RNA LINC00844 in CCA progression, explore the underlying molecular mechanisms, and to analyze the potential prognostic value of LINC00844 in CCA patients. Methods Expression of LINC00844 in CCA cell lines and tissues was examined by reverse transcription-quantitative PCR. Cell counting kit-8 assay was used to assess CCA cell proliferation, and the Transwell assay was used to evaluate tumor cell migration and invasion. miRNAs sponged by LINC00844 were predicted and confirmed using a luciferase reporter assay. Kaplan–Meier survival analysis was performed to evaluate the survival prognosis of CCA patients. Results The expression levels of LINC00844 were decreased in CCA tissues and cells. Overexpression of LINC00844 inhibited cell proliferation, migration and invasion in CCA cells. miR-19a-5p is directly targeted by LINC00844, mediating the inhibitory effects of LINC00844 on the proliferation, migration and invasion of CCA cells. LINC00844 and miR-19a-5p expression were associated with differentiation and tumor node metastasis stage in CCA patients. CCA patients with low LINC00844 expression or overexpression of miR-19a-5p had worse overall survival. Conclusion The expression levels of LINC00844 were decreased in both CCA tissues and cells, and high LINC00844 inhibited CCA cell proliferation, migration and invasion through sponging miR-19a-5p. Low LINC00844 and high miR-19a-5p expression were associated with worse overall survival in CCA patients. All the data suggested that the LINC00844/miR-19a-5p axis may provide novel therapeutic targets and prognostic biomarkers for CCA patients (AU)


Assuntos
Humanos , Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Ductos Biliares Intra-Hepáticos/metabolismo , Ductos Biliares Intra-Hepáticos/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética
6.
Gastroenterol. hepatol. (Ed. impr.) ; 47(1): 24-31, ene. 2024. ilus, tab, graf
Artigo em Inglês | IBECS | ID: ibc-229083

RESUMO

Background MicroRNAs (miRNAs) are a group of small non-coding RNAs that bind to the target mRNA and regulate gene expression. Recently circulating microRNAs were investigated as markers of diseases and therapeutic targets. Although various studies analyze the miRNA expression in liver disease, these studies on PFIC are few. Progressive familial intrahepatic cholestasis (PFIC) is a rare liver disease with autosomal recessive inheritance. Most children with PFIC progress to cirrhosis and liver failure and consequently need to have a liver transplant. The aim of this study is the investigation of the miR-19b and miR-let7b expression levels in Iranian PFIC children. Methods 25 PFIC patients, 25 healthy children and 25 Biliary Atresia patients were considered as case and two control groups respectively. Blood samples were obtained and Liver function tests (LFTs) were measured. After RNA extraction and cDNA synthesis, quantitative PCR was performed using specific primers for miR-19b and miR-let7b. The U6 gene is used as an internal control. Results qPCR on PFIC patients’ samples demonstrated that the miR-19b and the miR-let7b expression were significantly decreased in patients compared to the control groups, with a p-value<0.0001 and p-value=0.0006 receptively. Conclusion In conclusion, circulating micro-RNA like miR-19b and miR-let7b have a potential opportunity to be a non-invasive diagnostic marker or therapeutic target for PFIC in the future (AU)


Antecedentes Los microRNA (miRNA) son un grupo de pequeños RNA no codificantes que se unen al ARNm diana y regulan la expresión génica. Recientemente se han investigado los microRNA circulantes como marcadores de enfermedades y dianas terapéuticas. Aunque varios estudios analizan la expresión de miRNA en enfermedades hepáticas, estos estudios sobre PFIC son escasos. La colestasis intrahepática familiar progresiva (PFIC) es una enfermedad hepática rara con herencia autosómica recesiva. La mayoría de los niños con PFIC progresan a cirrosis e insuficiencia hepática y, en consecuencia, requieren de un trasplante de hígado. El objetivo de este trabajo es la investigación de los niveles de expresión de miR-19b y miR-17b en niños iraníes con PFIC. Métodos Se consideraron 25 pacientes con PFIC, 25 niños sanos y 25 pacientes con atresia biliar como grupos de casos y controles. Se obtuvieron muestras de sangre y se midieron las pruebas de función hepática (LFT). Después de la extracción de RNA y la síntesis de cDNA, se realizó PCR cuantitativa usando cebadores específicos para miR-19b y miR-17b. El gen U6 se utiliza como control interno. Resultados La qPCR en muestras de pacientes con PFIC demostró que la expresión de miR-19b y miR-17b disminuyó significativamente en los pacientes en comparación con dos grupos de control, con un valor de p<0,0001 y un valor de p=0,0006, receptivamente. Conclusión En conclusión, los micro-RNA circulantes, como miR-19b y miR-let7b, tienen una oportunidad potencial de ser un marcador de diagnóstico no invasivo o un objetivo terapéutico para PFIC en el futuro (AU)


Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Criança , Colestase Intra-Hepática/diagnóstico , Colestase Intra-Hepática/genética , Insuficiência Hepática , Fibrose , MicroRNAs/genética
7.
Clin. transl. oncol. (Print) ; 26(1): 1-15, jan. 2024.
Artigo em Inglês | IBECS | ID: ibc-229143

RESUMO

MicroRNAs (miRNAs) negatively affect gene expression by binding to their specific mRNAs resulting in either mRNA destruction or translational repression. The aberrant expression of various miRNAs has been associated with a number of human cancer. Oncogenic or tumor-suppressor miRNAs regulate a variety of pathways involved in the development of breast cancer (BC), including cell proliferation, apoptosis, metastasis, cancer recurrence, and chemoresistance. Variations in miRNA-encoding genes and their target genes lead to dysregulated gene expression resulting in the development and progression of BC. The various therapeutic approaches to treat the disease include chemotherapy, radiation therapy, surgical removal, hormone therapy, chemotherapy, and targeted biological therapy. The purpose of the current review is to explore the genetic variations in tumor-suppressor miRNA-encoding genes and their target genes in association with the disease development and prognosis. The therapeutic interventions targeting the variants for better disease outcomes have also been discussed (AU)


Assuntos
Humanos , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/terapia , Regulação Neoplásica da Expressão Gênica , Variação Genética , Genes Supressores de Tumor , MicroRNAs/genética , MicroRNAs/metabolismo , Recidiva Local de Neoplasia/genética
8.
Clin. transl. oncol. (Print) ; 26(1): 16-38, jan. 2024. ilus, tab
Artigo em Inglês | IBECS | ID: ibc-229144

RESUMO

Recent studies have revealed the impact of microRNAs (miRNAs) in the carcinogenic process. miR-424 is a miRNA whose role in this process is being to be identified. Experiments in the ovarian cancer, cervical cancer, hepatocellular carcinoma, neuroblastoma, breast cancer, osteosarcoma, intrahepatic cholangiocarcinoma, prostate cancer, endometrial cancer, non-small cell lung cancer, hemangioma and gastric cancer have reported down-regulation of miR-424. On the other hand, this miRNA has been found to be up-regulated in melanoma, laryngeal and esophageal squamous cell carcinomas, glioma, multiple myeloma and thyroid cancer. Expression of this miRNA is regulated by methylation status of its promoter. Besides, LINC00641, CCAT2, PVT1, LIN00657, LINC00511 and NNT-AS1 are among lncRNAs that act as molecular sponges for miR-424, thus regulating its expression. Moreover, several members of SNHG family of lncRNAs have been found to regulate expression of miR-424. This miRNA is also involved in the regulation of E2F transcription factors. The current review aims at summarization of the role of miR-424 in the process of cancer evolution and its impact on clinical outcome of patients in order to find appropriate markers for malignancies (AU)


Assuntos
Humanos , Carcinogênese/genética , Carcinogênese/patologia , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Esofágicas/genética , Neoplasias Pulmonares/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica
9.
Clin. transl. oncol. (Print) ; 26(1): 190-203, jan. 2024.
Artigo em Inglês | IBECS | ID: ibc-229157

RESUMO

Purpose This study intends to investigate the possible molecular mechanism of immune response and tumorigenesis in ovarian cancer cells, mediated by sirtuin 1 (SIRT1)-containing extracellular vesicles (EVs) derived from cancer-associated adipocytes (CAAs) (CAA-EVs). Methods Differentially expressed genes in EVs from CAAs were screened by RNA transcriptome sequencing, and the downstream pathway was predicted in silico. The binding between SIRT1 and CD24 was investigated by luciferase activity and ChIP-PCR assays. EVs were extracted from human ovarian cancer tissue-isolated CAAs, and the internalization of CCA-EVs by ovarian cancer cells was characterized. The ovarian cancer cell line was injected into mice to establish an animal model. Flow cytometry was performed to analyze the proportions of M1 and M2 macrophages, CD8+ T, T-reg, and CD4+ T cells. TUNEL staining was used to detect cell apoptosis in the mouse tumor tissues. ELISA detection was performed on immune-related factors in the serum of mice. Results CAA-EVs could deliver SIRT1 to ovarian cancer cells, thereby affecting the immune response of ovarian cancer cells in vitro and promoting tumorigenesis in vivo. SIRT1 could transcriptionally activate the expression of CD24, and CD24 could up-regulate Siglec-10 expression. CAA-EVs-SIRT1 activated the CD24/Siglec-10 axis and promoted CD8+ T cell apoptosis, thereby promoting tumorigenesis in mice. Conclusion CAA-EVs-mediated transfer of SIRT1 regulates the CD24/Siglec-10 axis to curb immune response and promote tumorigenesis of ovarian cancer cells (AU)


Assuntos
Humanos , Feminino , Vesículas Extracelulares , MicroRNAs/metabolismo , Neoplasias Ovarianas/patologia , Ácidos Siálicos , Adipócitos/metabolismo , Adipócitos/patologia , Carcinogênese/metabolismo , Linhagem Celular Tumoral , Transformação Celular Neoplásica/metabolismo , Imunidade , Lecitinas/metabolismo
10.
Clin. transl. oncol. (Print) ; 26(1): 245-259, jan. 2024.
Artigo em Inglês | IBECS | ID: ibc-229163

RESUMO

Purpose A substantial amount of evidence demonstrates suggests that long non-coding RNAs (lncRNAs) play a key role in the progression of various malignancies, cervical squamous cell carcinoma (CSCC) included. In our study, we deeply investigated the role and molecular mechanism of lncRNA NPHS2-6 in CSCC. Methods The expression level of gene and protein expression were measured by qRT-PCR and western blot. To test the cell proliferation and cell metastasis ability, we carried out the CCK-8 experiment, clone formation assay, transwell assay and wound healing, respectively. The interactivity among NPHS2-6, miR-1323 and SMC1B were co demonstrated using the bioinformatics tool, dual-luciferase reporter system, and RNA pulldown assay. The subcutaneous tumor model of nude mice was established to verify the results of previous studies at the in vivo. NPHS2-6 was upregulated in CSCC tissues and cells. Results NPHS2-6 deficiency significantly inhibited CSCC cell growth and EMT in vitro. In addition, NPHS2-6 deficiency also inhibited the growth of CSCC xenograft tumors in mice in vivo. Importantly, NPHS2-6 was a competing endogenous RNA (ceRNA) to increases SMC1B levels by binding to miR-1323, leading to activate the PI3K/Akt pathway, thereby exacerbating tumorigenesis of CSCC. Conclusions In conclusion, NPHS2-6/miR-1323/SMC1B/PI3K/Akt signaling accelerates the progression of CSCC, providing a new direction for the treatment strategy of CSCC (AU)


Assuntos
Animais , Feminino , Camundongos , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Uterinas/genética , Neoplasias Uterinas/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo
12.
Clin. transl. oncol. (Print) ; 25(12): 3321-3331, dec. 2023.
Artigo em Inglês | IBECS | ID: ibc-227279

RESUMO

CircRNA, the latest research hotspot in the field of RNA, is a special non-coding RNA molecule, which is unable to encode proteins and bind polyribosomes. As a regulatory molecule, circRNA participates in cancer cell generation and progression mainly through the mechanism of competitive endogenous RNA. In numerous regulated cancer organs, the thyroid and breast are both endocrine organs, and both are regulated by the hypothalamic pituitary gland axis. Thyroid cancer (TC) and breast cancer (BC) are both sexually prevalent in women and both are affected by hormones, thus they are intrinsically linked. In addition, recent epidemiological surveys have found that, early metastasis and recurrence of breast cancer remain the main cause of survival in breast cancer patients. Although at home and abroad, studies have shown that new targeted anti-tumor drugs with numerous tumor markers are gradually being used in the clinic, evidence for potential molecular mechanisms affecting its prognosis lacks clinical studies. Therefore, we search the relevant literature, and based on the latest domestic and international consensus, review the molecular mechanisms and regulation relevance of circRNA, compare the difference of the same circRNA in two tumors, to more deeply understand and lay the foundation for future clinical diagnostic, therapeutic and prognostic studies in large samples (AU)


Assuntos
Humanos , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , /genética , MicroRNAs/genética
13.
Clin. transl. oncol. (Print) ; 25(12): 3345-3356, dec. 2023.
Artigo em Inglês | IBECS | ID: ibc-227281

RESUMO

Despite recent therapy advances and a better understanding of colon cancer biology, it remains one of the major causes of death. The cancer stem cells, associated with the progression, metastasis, and recurrence of colon cancer, play a major role in promoting the development of tumour and are found to be chemo resistant. The stroma of the tumour, which makes up the bulk of the tumour mass, is composed of the tumour microenvironment. With the advent of theranostic and the development of personalised medicine, miRNAs are becoming increasingly important in the context of colon malignancies. A holistic understanding of the regulatory roles of miRNAs in cancer cells and cancer stem cells will allow us to design effective strategies to regulate miRNAs, which could lead to improved clinical translation and creating a potent colon cancer treatment strategy. In this review paper, we briefly discuss the history of miRNA as well as the mechanisms of miRNA and cancer stem cells that contribute to the tumour growth, apoptosis, and advancement of colon cancer. The usefulness of miRNA in colorectal cancer theranostic is further concisely reviewed. We conclude by holding a stance in addressing the prospects and possibilities for miRNA by the disclosure of recent theranostic approaches aimed at eradicating cancer stem cells and enhancing overall cancer treatment outcomes (AU)


Assuntos
Humanos , Transdução de Sinais/genética , Neoplasias do Colo/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Células-Tronco Neoplásicas/patologia , Microambiente Tumoral
14.
Clin. transl. oncol. (Print) ; 25(12): 3420-3430, dec. 2023.
Artigo em Inglês | IBECS | ID: ibc-227287

RESUMO

Background The lncRNA HOTAIR is frequently overexpressed in breast cancer tissues and plays an important role in the development of breast cancer. Here, we investigated the effect of the lncRNA HOTAIR on the biological behaviour of breast cancer cells and its molecular mechanism. Methods We investigated the level of HOTAIR in breast cancer and its clinical pathological characteristics by bioinformatic methods. Then, we evaluated the effects of HOTAIR and miRNA-1 expression on the biological behaviour of breast cancer cells by qPCR, Cell Counting Kit-8 (CCK-8) assay, clonogenic assays, Transwell assay and flow cytometry for cell proliferation, invasion migration and apoptosis, and cell cycle analysis. Finally, the target genes of the lncRNA HOTAIR/miR-1/GOLPH3 regulatory axis were validated by luciferase reports. Results The expression of HOTAIR in breast cancer tissues was significantly higher than that in normal breast tissues (P < 0.05). Silencing of HOTAIR suppressed cell proliferation, invasion and migration, promoted apoptosis and induced G1 phase block in breast cancer (P < 0.0001). We also verified that miR-1 is a target of HOTAIR and that GOLPH3 is a target of miR-1 by luciferase reporter assays (P < 0.001). Conclusions The expression of HOTAIR was significantly elevated in breast cancer tissues. Reducing the expression of HOTAIR inhibited the proliferation, invasion and migration of breast cancer cells and promoted apoptosis, and the mechanism was mainly the effect of the lncRNA HOTAIR/miR-1/GOLPH3 regulatory axis on the biological behaviour of breast cancer cells (AU)


Assuntos
Humanos , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Luciferases/metabolismo , Proteínas de Membrana/genética
15.
Clin. transl. oncol. (Print) ; 25(11): 3152-3164, 11 nov. 2023. graf
Artigo em Inglês | IBECS | ID: ibc-226840

RESUMO

Objective Local recurrence, distant metastasis, and perineural invasion (PNI) viciously occur in salivary adenoid cystic carcinoma (SACC), resulting in a poor prognosis. This study aimed to explore the mechanism by which circular RNA RNF111 (circ-RNF111) regulates PNI in SACC by targeting the miR-361-5p/high mobility group box 2 (HMGB2) axis. Method Circ-RNF111 and HMGB2 were highly expressed in SACC specimens, while miR-361-5p was underexpressed. Functional experiments showed that ablating circ-RNF111 or promoting miR-361-5p hindered the biological functions and PNI of SACC-LM cells. Results HMGB2 overexpression induced the reversal of SACC-LM cell biological functions and PNI caused by circ-RNF111 knockout. Furthermore, reduction of circ-RNF111 suppressed PNI in a SACC xenograft model. Circ-RNF111 regulated HMGB2 expression through targeted modulation of miR-361-5p. Conclusion Taken together, circ-RNF111 stimulates PNI in SACC by miR-361-5p/HMGB2 axis and may serve as a potential therapeutic target for SACC (AU)


Assuntos
Humanos , Carcinoma Adenoide Cístico/genética , Carcinoma Adenoide Cístico/metabolismo , Proteína HMGB2/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias das Glândulas Salivares/genética , Neoplasias das Glândulas Salivares/metabolismo , Neoplasias das Glândulas Salivares/patologia , Carcinoma Adenoide Cístico/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Invasividade Neoplásica/genética , Proteínas Nucleares/metabolismo , /genética , Fatores de Transcrição/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo
16.
Clin. transl. oncol. (Print) ; 25(11): 3174-3187, 11 nov. 2023.
Artigo em Inglês | IBECS | ID: ibc-226842

RESUMO

Introduction In the present study, we sought to clarify the role of LINC01119 delivered by cancer-associated adipocytes (CAAs)-derived exosomes (CAA-Exo) and its mechanistic actions in ovarian cancer (OC). Materials and methods The expression of LINC01119 was determined in OC, and the relationship between LINC01119 expression and the prognosis of OC patients was analyzed. Besides, 3D co-culture cell models were constructed using green fluorescent protein-labeled OC cells and red fluorescent protein-labeled mature adipocytes. Mature adipocytes were co-cultured with OC cells to induce CAA. Macrophages treated with CAA-Exo were co-cultured with SKOV3 cells following ectopic expression and depletion experiments of LINC01119 and SOCS5 to detect M2 polarization of macrophages, PD-L1 level, proliferation of CD3+ T cells, and cytotoxicity of T cells to SKOV3 cells. Results LINC01119 was elevated in the plasma Exo of OC patients, which was related to shorter overall survival in OC patients. LINC01119 expression was increased in CAA-Exo, which could upregulate SOCS5 in OC. Finally, CAA-Exo carrying LINC01119 induced M2 polarization of macrophages to promote immune escape in OC, as evidenced by inhibited CD3+ T cell proliferation, increased PD-L1 level, and attenuated T cell toxicity to SKOV3 cells. Conclusion In conclusion, the key findings of the current study demonstrated the promoting effects of CAA-Exo containing LINC01119 mediating SOCS5 on M2 polarization of macrophages and immune escape in OC (AU)


Assuntos
Humanos , Feminino , Exossomos/metabolismo , MicroRNAs/metabolismo , Neoplasias Ovarianas/metabolismo , Adipócitos/metabolismo , Antígeno B7-H1/metabolismo , Linhagem Celular Tumoral , Técnicas de Cocultura , Macrófagos/metabolismo , Transdução de Sinais
17.
Clin. transl. oncol. (Print) ; 25(11): 3217-3229, 11 nov. 2023. graf
Artigo em Inglês | IBECS | ID: ibc-226845

RESUMO

Background Radiotherapy is widely employed in colorectal cancer (CRC) treatment but is often compromised by developed radioresistance. This study explored the mechanism of long non-coding RNA ovarian tumor domain containing 6B-antisense RNA1 (lncRNA OTUD6B-AS1) in CRC radioresistance through tripartite motif 16 (TRIM16). Methods CRC and non-cancerous tissues were collected and radioresistant CRC cells were established, with real-time quantitative polymerase chain reaction to determine gene expression in tissues and cells. Radioresistance was evaluated by cell counting kit-8 assay and immunofluorescence (γ-H2AX) and ferroptosis was tested by Western blot assay (ACSL4/GPX4) and assay kits (Fe2+/ROS/MDA/GSH). The association between ferroptosis and lncRNA OTUD6B-AS1-inhibited radioresistance was testified using ferroptosis inhibitor. The subcellular localization of lncRNA OTUD6B-AS1 was tested by the nuclear/cytoplasmic fractionation assay, with RNA immunoprecipitation assay to validate gene interactions. Rescue experiments were conducted to analyze the role of TRIM16 in CRC radioresistance. Results LncRNA OTUD6B-AS1 and TRIM16 were poorly expressed (P < 0.01) in CRC tissues and cells and further decreased (P < 0.01) in radioresistant CRC cells. OTUD6B-AS1 overexpression decreased cell survival (P < 0.01), increased γ-H2AX levels (P < 0.01), and elevated ferroptosis and oxidative stress (P < 0.01) after X-ray radiation. Ferroptosis inhibitor attenuated radioresistance (P < 0.01) caused by lncRNA OTUD6B-AS1 overexpression. LncRNA OTUD6B-AS1 stabilized TRIM16 mRNA via binding to HuR. TRIM16 knockdown reduced ferroptosis and increased radioresistance (P < 0.05). Conclusion OTUD6B-AS1 overexpression stabilized TRIM16 via binding to HuR and increased GPX4-mediated ferroptosis, thus attenuating CRC radioresistance. Our study provided a new rationale for the treatment of CRC (AU)


Assuntos
Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/radioterapia , MicroRNAs/genética , RNA Longo não Codificante/genética , Neoplasias Colorretais/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Proteínas com Motivo Tripartido , Ubiquitina-Proteína Ligases
18.
Clin. transl. oncol. (Print) ; 25(11): 3252-3262, 11 nov. 2023.
Artigo em Inglês | IBECS | ID: ibc-226848

RESUMO

Objective The significance of circular RNAs (circRNAs) has been identified in the progression of non-small cell lung cancer (NSCLC). Consistently, our study probed the functional actions of hsa_circ_0102899 (circ_0102899) in NSCLC cells. Methods circ_0102899 expression was checked in NSCLC tissues, as well as its correlation with clinical characteristics of patients, Using A459 cells, transfection to alter gene expression was performed, thus measuring the changes of proliferation, apoptosis, migration, and apoptosis, as well as epithelial–mesenchymal transition (EMT)-related proteins. circ_0102899’s effects in vivo were validated by tumor xenograft assay. Finally, the regulatory mechanism of circ_0102899 was investigated. Results circ_0102899 indicated a high-expression level in NSCLC tissues which was associated with NSCLC tumor characteristics. Functionally, circ_0102899 knockdown not only inhibited the growth and EMT process of NSCLC cells, but also inhibited tumor formation in vivo. In terms of the regulatory mechanism, circ_0102899 had a binding to miR-885-5p to target eukaryotic translation initiation factor 4γ2 (EIF4G2). circ_0102899 mediated miR-885–5/EIF4G2 axis to accelerate the process of cell malignant behavior in NSCLC. Conclusion circ_0102899 promotes EMT and metastasis in NSCLC by regulating the miR-885-5p/EIF4G2 axis (AU)


Assuntos
Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , MicroRNAs/genética , Apoptose , Linhagem Celular Tumoral , Proliferação de Células
19.
Clin. transl. oncol. (Print) ; 25(11): 3296-3306, 11 nov. 2023.
Artigo em Inglês | IBECS | ID: ibc-226852

RESUMO

Purpose The prognosis of advanced gastric cancer (GC) remains poor. It is urgent and necessary to find suitable prognostic markers. miR-619-5p is highly expressed in GC. However, the value of miR-619-5p and its target genes as prognostic biomarkers of GC is unclear. Methods RT-PCR was performed to verify the expression of miR-619-5p in GC cell lines and their exosomes. Western blotting and transmission electron microscope were used to identify exosomes. The target genes of miR-619-5p were predicted by RNA22 and TargetScan. The differentially expressed genes (DEGs) and prognosis-related genes (PRGs) were obtained using The Cancer Genome Atlas (TCGA) database. The DAVID database was used to analyse pathway enrichment and functional annotation of common target genes. The STRING database and Cytoscape software were used to screen key genes and visualize their functional modules. The survival analysis was conducted using TCGA and Kaplan–Meier Plotter (KMP) databases. Finally, a prognostic model was constructed on the foundation of the key genes to assess the reliability of the screening process. Results The expression of miR-619-5p in GC cells and their exosomes was proved to be significantly higher than that in normal cell lines. There are 129 common target genes involved in 3 pathways and 28 functional annotations. Finally, nine key target genes of GC (BRCA1, RAD51, KIF11, ERCC6L, BRIP1, TIMELESS, CDC25A, CLSPN and NCAPG2) were identified, and a prognostic model was successfully constructed with a good predictive ability. Conclusions The model of 9-gene signature could effectively predict the prognosis of GC, and have great potential to be novel prognostic factors and therapeutic targets for patients with GC (AU)


Assuntos
Humanos , Biologia Computacional , MicroRNAs/genética , Neoplasias Gástricas , Biomarcadores Tumorais , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Cromossômicas não Histona , Reprodutibilidade dos Testes , Prognóstico
20.
Arch. bronconeumol. (Ed. impr.) ; 59(10): 629-637, oct. 2023. tab, graf
Artigo em Inglês | IBECS | ID: ibc-226190

RESUMO

Introduction: There is still a debate for the link between obstructive sleep apnoea (OSA) and cancer. The mechanisms underlying this causality are poorly understood. Several miRNAs are involved in cancer development and progression with expression being influenced by hypoxia. The aims of this work were (i) to compare miRNAs expression in controls versus patients affected by OSA without or with cancer (ONCO-OSA) and (ii) in colorectal cancer cells exposed to intermittent hypoxia (IH), to evaluate miRNAs impact on tumor progression in vitro. Methods: We detected miRNAs by qRT-PCR in patients’ sera and in CaCo2 cells exposed to 2–32h of IH with or without acriflavine (ACF), a HIF-1 inhibitor. Viability and transwell invasion test were applied to investigate the proliferation and migration of CaCo2 exposed to IH and treated with miRNA inhibitors or acriflavine. HIF-1α activity was evaluated in CaCo2 cells after IH. Results: The levels of miR-21, miR-26a and miR-210 increased in OSA and ONCO-OSA patients compared to controls. MiR-23b increased in ONCO-OSA patients, and miR-27b and miR-145 increased in OSA but not ONCO-OSA patients. MiR-21, miR-26a, miR-23b and miR-210 increased in cells after IH. IH stimulated cell proliferation and migration. This effect was reduced after either miRNA inhibition or acriflavine treatment. MiRNA inhibition reduces HIF-1α gene expression. Conversely, acriflavine reduced the expression of these miRNAs. Conclusions: We identified a signature of miRNAs, induced by the IH environment. They could be implicated in cancer development and progression through a regulatory loop involving HIF-1. (AU)


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , MicroRNAs/genética , Neoplasias , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/genética , Hipóxia , Células CACO-2 , Acriflavina
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