Abstract
Our previous study shows that Calpain 6 (CAPN6) expression is regulated by PI3K-Akt in liver cancer through POU2F1 and CAPN6 which promote cell proliferation and inhibit apoptosis of liver cancer cells. microRNAs (miRNAs) plays important roles in regulation of gene expression. However, whether miRNAs regulates CAPN6 expression and its cellular function is still unknown. This study aims to investigate how miRNAs regulate liver cancer apoptosis through POU2F1-CAPN6. It was verified that POU2F1 could promote cell proliferation and inhibit apoptosis through CAPN6. Using methods of bioinformatics, miR-449a was predicted as a potential regulator of both CAPN6 and POU2F1. It was verified that CAPN6 and POU2F1 were the target genes of miR-449a by luciferase assay. CAPN6 and POU2F1 protein and mRNA levels decreased in liver cancer cells with miR-449a overexpression using western blot and real time RT-PCR assays. miR-449a expression was lower in liver cancer tissues compared with their normal ones, so did the cells. Overexpression of miR-449a inhibited cell proliferation, induced G1 phase arrest and cell apoptosis in liver cancer. Further research demonstrated that miR-449a inhibited cancer cell proliferation and induced apoptosis via suppressing both POU2F1 and CAPN6. The study indicated that miR-449a functions as a tumor inhibitor in liver cancer by decreasing POU2F1 and CAPN6 expression in liver cancer.
Highlights
Liver cancer is one of the most common tumor, which is the third cause of cancer-related death worldwide [1]
Calpain 6 (CAPN6) and POU2F1 mRNA increased in the cells with anti-miR-449a (Figure 2G and 2H)
CAPN6 is overexpressed in many types of tumor and its function in tumor includes leading to apoptosis resistance, promoting cell proliferation and angiogenesis
Summary
Liver cancer is one of the most common tumor, which is the third cause of cancer-related death worldwide [1]. Hepatic resection and transplantation are relative effective therapeutic methods in liver cancer, tumor recurrence rate is still very high [2, 3]. There are no well-established effective adjuvant therapeutics for liver cancer [2]. Previous reports show that the cellular function of CAPN6 includes the regulation of cell microtubule dynamics and cytoskeletal organization in embryonic tissues [7,8,9]. It may involve in tumorigenesis such as inhibiting cell apoptosis and promoting angiogenesis [10]. Its regulatory mechanism by microRNAs (miRNAs) is not known
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