RESUMO
Cancer is frequently caused by microRNAs, which control post-transcriptional levels of gene expression by binding to target mRNAs. MiR-29a-3p has recently been shown to play a twofold function in the majority of malignancies, including colorectal cancer (CRC), according to mounting evidence. Here, we not only briefly summarize such connection between miR-29a-3p and cancers, but aslo primarily evaluate the miR-29a-3p expression pattern, clinical applicability, and molecular mechanisms in CRC to provide a guide for future studies. This review established the diagnostic and prognostic value of miR-29a-3p abnormalty in a variety of clinical samples for CRC. Furthermore, current molecular mechanisms of miR-29a-3p for regulating cancerous biological processes such growth, invasion, metastasis, the epithelial-mesenchymal transformation process, and immunomodulation through its upstream regulatory factors and downstream targeted genes were briefly explored. More specifically, miR-29a-3p has been linked to a few medications that have been shown to have anticancer benefits. To sum up, miR-29a-3p is a promising biomarker and prospective therapeutic target for the diagnosis and prognosis of CRC, but further research is still needed to establish a theoretical basis for more practical applications.
Assuntos
Neoplasias Colorretais , MicroRNAs , Humanos , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , MicroRNAs/metabolismo , Prognóstico , Biomarcadores , Neoplasias Colorretais/genética , Neoplasias Colorretais/terapia , Neoplasias Colorretais/patologia , Proliferação de Células/genéticaRESUMO
OBJECTIVE: Collagen type IV alpha 1 (COL4A1) exerts tumor-promoting functions in several tumors. However, its role in liver cancer remains not fully understood. Hence, this study aims to investigate the role of COL4A1 in regulating liver cancer cell behaviors and to validate its upstream regulatory mechanism. METHODS: Expression of xeroderma pigmentosum D (XPD) and COL4A1 was examined by qRT-PCR and western blot. Cell proliferation, migration, and invasion were evaluated. The protein levels of N-cadherin, vimentin, and E-cadherin were determined by western blot to evaluate epithelial-mesenchymal transition (EMT). The interaction between miR-29a-3p and COL4A1 was analyzed by luciferase reporter assay. RESULTS: COL4A1 overexpression significantly promoted cell proliferation, migration, invasion, and EMT in Hep3B cells. In contrast, COL4A1 silencing yielded the opposite effects in HepG2 cells. Expression of COL4A1 was increased, whereas expression of XPD and miR-29a-3p was decreased in HCC tissues compared to controls. COL4A1 mRNA level was negatively correlated with expression of XPD and miR-29a-3p in HCC tissues. Furthermore, XPD silencing-mediated up-regulation of COL4A1 expression was attenuated by miR-29a-3p mimic. Moreover, miR-29a-3p mimic inhibited Hep3B cell proliferation, migration, and invasion by directly targeting COL4A1. CONCLUSION: COL4A1 is negatively regulated by XPD-miR-29a-3p axis and promotes liver cancer progression in vitro.
Assuntos
Carcinoma Hepatocelular/metabolismo , Colágeno Tipo IV/metabolismo , Neoplasias Hepáticas/metabolismo , MicroRNAs/metabolismo , Proteína Grupo D do Xeroderma Pigmentoso/metabolismo , Antígenos CD/análise , Caderinas/análise , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Colágeno Tipo IV/genética , Transição Epitelial-Mesenquimal , Feminino , Inativação Gênica , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Vimentina/análiseRESUMO
Sevoflurane (SEVO) is widely applied as an anesthetic, which exerts antitumor capacity in various cancers, including hepatocellular carcinoma (HCC). Previous studies indicated that long non-coding RNA KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) was upregulated, while microRNA-29a-3p (miR-29a-3p) was downregulated in HCC. Thus, we aimed to explore the roles of KCNQ1OT1 and miR-29a-3p in HCC cells exposed to SEVO. Cell proliferation, apoptosis, migration, and invasion were assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry, and transwell assays, respectively. The levels of genes were determined by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. Furthermore, the interaction between miR-29a-3p and KCNQ1OT1 or chromebox protein homolog 3 (CBX3) was predicted by Starbase or Targetscan, and then confirmed by dual-luciferase reporter assay. We found that the levels of KCNQ1OT1 and CBX3 were decreased, while miR-29a-3p was increased in SEVO-treated HCC cells. KCNQ1OT1 overexpression weakened the inhibitory effects of SEVO on HCC cell proliferation, apoptosis, migration, and invasion. Interestingly, KCNQ1OT1 bound to miR-29a-3p, and miR-29a-3p targeted CBX3. KCNQ1OT1 upregulated CBX3 level by repressing miR-29a-3p expression. Furthermore, KCNQ1OT1 exerted tumor promotion in HCC cells via suppressing miR-29a-3p to regulate CBX3 expression. Collectively, our findings demonstrated that KCNQ1OT1 regulated the antitumor effects of SEVO on HCC cells through modulating the miR-29a-3p/CBX3 axis, providing a theoretical basis for the treatment of HCC.