Abstract
Increasing evidence suggests that aberrant expression of certain microRNAs (miRNAs) may participate in the genesis and progression of tumors. Several studies have indicated that miR-1247-5p plays different roles in various types of cancer cells. The effects of miR-1247-5p on human hepatocellular carcinoma (HCC) cells are elusive. In the present study, we investigated the effects of miR-1247-5p on the progression of HCC. The transcript of miR-1247-5p was markedly downregulated in clinical samples of patients with HCC and HCC cell lines, and ectopic overexpression of miR‑1247-5p markedly inhibited the proliferation and invasion of HepG2 cells, induced cell apoptosis invitro, and suppressed the growth of transplanted tumors invivo. Wnt3 was found to be a potential target of miR-1247-5p and overexpression of miR-1247-5p was able to significantly downregulate the expression of Wnt3 by directly targeting the 3'UTR of this gene, which was verified by luciferase reporter assay and western blotting. Furthermore, we found that the miR-1247-5p gene was hypermethylated in HepG2 cells, and the transcript of miR-1247-5p was increased significantly after treatment with the demethylation drug 5-azacytidine. These findings demonstrated that miR-1247-5p functions as a tumor suppressor in human HCC by targeting Wnt3 and that the expression of miR-1247-5p can be regulated by DNA methylation, which indicates that miR-1247-5p has the potential to be a therapeutic target as well as a diagnostic marker of HCC.
Highlights
Hepatocellular carcinoma (HCC) is a common malignant tumor of the digestive tract [1]
The results revealed that the mRNA expression of miR-1247-5p was significantly decreased in the HCC cell lines, HepG2 (0.721±0.090%; p
Due to the existence of miR-1247-5p in sera, it is suggested that the detection of the expression of miR-1247-5p in sera can be used as a non-invasive approach for the early diagnosis of HCC
Summary
Hepatocellular carcinoma (HCC) is a common malignant tumor of the digestive tract [1]. The role of epigenetic regulation, DNA methylation and the aberrant expression of miRNAs, in the occurrence and development of cancers is gradually being recognized [2,3]. MicroRNAs (miRNAs) are single stranded, small noncoding RNAs of 18-25 nucleotides in length. They can negatively regulate gene expression through base-pairing to the 3' untranslated region (3'UTR) of target mRNAs, resulting in translation inhibition or mRNA degradation [4,5,6]. More and more studies suggest that beyond involvement in various biological processes, including cell growth, differentiation and apoptosis [8,9,10], dysregulation or dysfunction of miRNAs contributes to the genesis and progression of cancer. It is expected that by exploring the role of miRNAs in tumorigenesis and progression a new approach for the early diagnosis and treatment of HCC may be provided
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