Abstract
Increasing evidence has suggested that microRNAs (miRNAs) play an important role in the initiation and progression of hepatocellular carcinoma (HCC). Here, we identified a novel tumor suppressive miRNA, miR-377, and investigated its role in HCC. The expression of miR-377 in HCC tissues and cell lines was detected by real-time reverse-transcription PCR. The effects of miR-377 on HCC cell proliferation and invasion were also investigated. Western blot and luciferase reporter assay were used to identify the direct and functional target of miR-377. The expression of miR-377 was markedly downregulated in human HCC tissues and cell lines. MiR-377 can dramatically inhibit cell growth and invasion in HCC cells. Subsequent investigation revealed that T lymphoma invasion and metastasis 1 (TIAM1) was a direct and functional target of miR-377 in HCC cells. Overexpression of miR-377 impaired TIAM1-induced promotion of proliferation and invasion in HCC cells. Finally, miR-377 is inversely correlated with TIAM1 expression in human HCC tissues. These findings reveal that miR-377 functions as a tumor suppressor and inhibits the proliferation and invasion of HCC cells by targeting TIAM1, which may consequently serve as a therapeutic target for HCC patients.
Highlights
Hepatocellular carcinoma (HCC) is one of the most aggressive and common malignancies, with high mortality and prevalence rates in East Asian countries including China[1]
Over the past several years, it has become clear that deregulated of miRNAs contribute to the development of most human cancers such as gastric cancer, bladder cancer and breast cancer, which they act as either oncogenes or tumor suppressors[20,21,22,23]
We investigated the role of miR-377 in human HCC development
Summary
Hepatocellular carcinoma (HCC) is one of the most aggressive and common malignancies, with high mortality and prevalence rates in East Asian countries including China[1]. The 5-year survival rate of HCC patients is still only approximately 5%, with exceeding 600,000 people dying of HCC each year[2]. Increasing evidences have suggested that miRNAs participate in the regulation of diverse processes such as tumor initiation, promotion, and progression, and their deregulation or dysfunction plays critical roles in cancer development and clinical outcomes of cancer patients[10,11,12,13,14]. We explored the potential roles of miR-377 in HCC development. The roles of miR-377 in HCC development and the underlying mechanisms were investigated. Our data indicate the role of miR-377 in the control of cell growth and invasion in HCC, and suggest the potential therapeutic application of miR-377 for HCC patients
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