Abstract
Aberrant expression of microRNAs (miRNAs) and its dysfunction have been revealed as crucial modulators of cancer initiation and progression. MiR-129-2 has been reported to play a tumor suppressive role in different human malignancies. Here, we demonstrated that miR-129-2 was significantly decreased in hepatocellular carcinoma (HCC) tissues and cell lines. Furthermore, miR-129-2 was expressed at significant lower levels in aggressive and recurrent tumor tissues. Clinical analysis indicated that miR-129-2 expression was inversely correlated with venous infiltration, high Edmondson-Steiner grading and advanced tumor-node-metastasis (TNM) stage in HCC. Notably, miR-129-2 was an independent prognostic factor for indicating overall survival (OS) and disease-free survival (DFS) of HCC patients. Ectopic expression of miR-129-2 inhibited cell migration and invasion in vitro and in vivo. Furthermore, we confirmed that high mobility group box 1 (HMGB1) was a direct target of miR-129-2, and it abrogated the function of miR-129-2 in HCC. Mechanistic investigations showed that miR-129-2 overexpression inhibited AKT phosphorylation at Ser473 and decreased the expression of matrix metalloproteinase2/9 (MMP2/9). Upregulation of p-AKT abolished the decreased cell migration and invasion induced by miR-129-2 in HCC. Whereas inhibition of Akt phosphorylation significantly decreased HMGB1-enhanced HCC cell migration and invasion. Moreover, we found that miR-129-2 was downregulated by DNA methylation, and demethylation of miR-129-2 increased miR-129-2 expression in HCC cells and resulted in significant inhibitory effects on cell migration and invasion. In conclusion, miR-129-2 may serve as a prognostic indicator for HCC patients and exerts tumor suppressive role, at least in part, by inhibiting HMGB1.
Highlights
Hepatocellular carcinoma (HCC) is one of the most common aggressive malignancies and the thirdmost common cause of cancer-related death worldwide [1]
Clinical analysis revealed that miR-129-2 was expressed at significantly lower levels in hepatocellular carcinoma (HCC) patients with multiple tumor nodes, venous infiltration, high Edmondson-Steiner grading and advanced TNM tumor stage
These results suggest that the reduced expression of miR-129-2 is correlated with poor prognostic features in HCC
Summary
Hepatocellular carcinoma (HCC) is one of the most common aggressive malignancies and the thirdmost common cause of cancer-related death worldwide [1]. Despite the advances in diagnosis and treatment, the majority of patients with HCC have an extremely dismal prognosis due to the high frequency of tumor recurrence or distant metastasis after surgical resection [2]. A better understanding of the underlying molecular mechanisms involved in the pathogenesis and progression of HCC is extremely important for the development of more effective therapeutic approaches for the treatment of patients with HCC. Previous studies have identified the critical role of miRNAs in human cancers and suggest that deregulation of miRNAs is involved in tumor development and progression by modulating the expression of oncogenes or tumor suppressors [12]. We speculate whether methylation alteration may occur in miRNAs, resulting in deregulation of its target genes in cancer cells
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
