Abstract
microRNAs (miRNAs) are negative regulators of gene expression and can function as tumor suppressors or oncogenes. Several miRNAs are associated with the development of hepatocellular carcinoma (HCC). miR-96 has been closely associated with cell proliferation and clonogenicity. Upregulation of miR-96 has been observed in various types of cancer. However, the biological function of miR-96 in hepatocarcinogenesis remains largely unknown. In this study, we demonstrated that miR-96 was upregulated in HCC and inhibition of miR-96 significantly suppressed HCC cell proliferation and colony formation. The expression levels of forkhead box O1 (FOXO1) and forkhead box O3a (FOXO3a) were upregulated when miR-96 was inhibited in HCC cells and the inhibition of FOXO1 and FOXO3a promoted HCC cell proliferation and colony formation. Collectively, these data reveal an important contribution of miR-96 to hepatocarcinogenesis and suggest a role for FOXO1 and FOXO3a dysregulation in this process. Thus, the use of a synthetic inhibitor of miR-96 may be a promising approach for the treatment of HCC.
Highlights
Hepatocellular carcinoma (HCC), the major type of liver cancer, is the fifth most frequent neoplasm and the third most common cause of cancer-related mortality in the world, in Asia and sub-Saharan Africa [1]
To assess whether Small interfering RNAs (siRNAs) could alter the expression of forkhead box O1 (FOXO1) and forkhead box O3a (FOXO3a) in HCC cells, we investigated the expression of FOXO1 and FOXO3a in HepG2 cells transfected with FOXO1and FOXO3a-specific siRNAs, or a negative control
Discussion miRNAs are involved in critical biological processes, including development, differentiation, apoptosis, and proliferation, through imperfect pairing with target messenger RNAs of protein-coding genes and transcriptional or post-transcriptional regulation of their expression
Summary
Hepatocellular carcinoma (HCC), the major type of liver cancer, is the fifth most frequent neoplasm and the third most common cause of cancer-related mortality in the world, in Asia and sub-Saharan Africa [1]. MiRNAs typically regulate post-transcriptional gene expression by interacting with sequences within the 3'-untranslational region (3'-UTR) of the target mRNA and play important roles in a variety of biological processes, including cell cycle regulation, cell differentiation, proliferation and apoptosis [5,6]. 50% of the genes that encode miRNAs reside in cancer-associated genomic regions or fragile sites and this fact highlights the importance of miRNAs in tumorigenesis [8]. MiR-96 has been recognized as an oncogenic miRNA that is upregulated in various types of cancer [9,10,11]. Recent studies identified the deregulation of miR-96 as being significantly associated with different risk factors for HCC, including HBV infection and alcohol consumption. MiR-96 was upregulated in several HCC cell lines [12]
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