Micro RNA miR-1303 Promotion of Proliferation, Migration and Invasion of Human Liver Cancer Cells Is Enhanced by Low Talin 1 (TLN1) Expression

Abstract

Background/Aim: Liver cancer is the third-most lethal cancer worldwide. Abnormal expression of microRNAs (miRNAs) modulates gene expression to exert oncogenic or tumor-suppressive effects in liver cancer. However, the biological role of miR-1303 in the progression of liver cancer and its regulatory mechanism has not been elucidated. Materials and Methods: The expression levels of miR-1303 were measured in liver-cancer tissues of patients and cell lines by RT-qPCR. Huh-7 and HepG2 liver-cancer cells were co-transfected by TLN1 and miR-1303 constructs. Cell viability was measured by the CCk-8 assay and colony-formation assay. Flow cytometry was used to measure cell apoptosis. Cell migration and invasion were determined by wound-healing and transwell-chamber assays. RT-PCR and western-blotting were used to determine miR-1303 inhibitor-associated marker expression, such as Bax, cleavedcaspase-3 and cleaved-caspase-9. Results: miR-1303 expression was strongly up-regulated in liver-cancer tissues and cells. Knockdown of miR-1303 attenuated cell proliferation, migration and invasion, and induced apoptosis in liver-cancer cells. Talin 1 (TLN1) and miR-1303 expression were negatively correlated, possibly by miR-1303 targeting the TLN1 gene. TLN1 expression enhanced the efficacy of an miR-1303 inhibitor to reduce liver-cancer cell proliferation and invasion. Conclusion: miR-1303 plays an important role in liver cancer, which is inhibited by TLN1 expression.Liver cancer is the third-most lethal cancer worldwide and the second-largest cancer-related cause of death in China (1). The long-term survival rate for liver-cancer patients remains poor due to lack of effective treatment (2, 3) . A greater understanding of the potential mechanism and progression of liver cancer is vital for developing more effective therapies.Micro-RNAs (miRNAs) are a class of small noncoding RNAs with a length of approximately 20-24 nucleotides. miRNAs play a large part in modulating the expression of diverse genes participating in the progression of numerous cancer types, via regulating mRNA expression (4-6). Knockdown of miRNAs which target proto-oncogenes and ectopic expression of oncogenic miRNA, can inhibit or enhance cancer progression, respectively (7-11). miR-20b, miR-27a and miR-181a which regulate HIPK2, HIF1A and MDR1, respectively, were expressed in gastric cancer during chemotherapy (12). miRNAs are candidate biomarkers for diagnosis or prognosis of pancreatic cancer which are in critical need (13). miRNAs in the cells of the tumor microenvironment, have been suggested as a target for liver cancer ( 14). miR-182-5p promotes hepatocellular carcinoma progression by repressing FOXO3a (15). miR-3662 suppresses liver-cancer growth via inhibition of the HIF-1αmediated Warburg Effect (16). miR-3 inhibited liver-cancer progression by targeting XRCC5 through the PI3K/AKT signaling pathway (17).miRNA-1303 has been shown to promote a number of different cancer types (18,19). However, the role of miR-1303 in liver cancer remains poorly understood. T...