miRNA-320a inhibits tumor proliferation and invasion by targeting c-Myc in human hepatocellular carcinoma

Abstract

BackgroundDownregulated expression levels of microRNA-320a (miR-320a) were found in primary breast cancers and colorectal cancer. Previous findings indicated that miRNA-320a may involve in the cancer development. In this study, we explored the roles of miR-320a by targeting c-Myc in the tumor growth of hepatocellular carcinoma (HCC).MethodsQuantitative reverse-transcription polymerase chain reaction (qRT-PCR) was performed to detect the expression of miR-320a in 50 HCC tissues and four HCC cells. Luciferase reporter assay was conducted to confirm the direct downstream target of miR-320a in HEK-293 cells. The effect of miR-320a on endogenous c-Myc expression was investigated by transfecting miR-320a mimics into HepG2 and QGY-7703 cell lines. The c-Myc and miR-320a expressions were analyzed by immunohistochemistry (IHC) and qRT-PCR in the same HCC tissues. Furthermore, the biological functional correlation of miR-320a with c-Myc was determined by studying the effect of miR-320a mimics or c-Myc small interfering RNA (siRNA) on HCC cell proliferation and invasion.ResultsThe expression of miR-320a was downregulated in 50 HCC tissues and 4 HCC cells. Luciferase assay revealed that c-Myc is a direct target of miR-320a. IHC and Western blot analysis showed that the c-Myc expression was inhibited by miR-320a in HCC tissues and cell lines. Upregulation of miR-320a suppressed the HCC cell proliferation and invasion capacity induced by inhibiting c-Myc, and the results were consistent with the effects of c-Myc siRNA on tumor suppression. These results revealed that miRNA-320a inhibits tumor proliferation and invasion by targeting c-Myc in HCC cells.ConclusionOur results showed that miR-320a functions as a tumor suppressor in HCC. By targeting c-Myc directly, miR-320a inhibits the HCC cell growth. Our studies provide evidence of miR-320a as a potentially target for HCC treatment.

Long non‐coding RNA SUMO1P3 promotes hepatocellular carcinoma progression through activating Wnt/β‐catenin signalling pathway by targeting miR‐320a

“…SUMO1P3 could negatively regulate the expression of miR‐320a in HCC. The up‐regulation of SUMO1P3 resulted in the down‐regulation of miR‐320a , which could promote HCC cell proliferation and invasion, thus contributing to malignant growth and metastasis . Our results were in line with those from published articles.…”

“…Taken together, SUMO1P3 contributed to malignant progression of HCC through activating Wnt/β‐catenin pathway via negatively regulating miR‐320a . However, the study carried out by Xie et al demonstrated that miR‐320a played anti‐tumour action in HCC through directly targeting c‐Myc. In addition, HMGB1 was confirmed to be a targeted gene of miR‐320a in HCC .…”

Circulating microRNA-34 family low expression correlates with poor prognosis in patients with non-small cell lung cancer

“…coding RNA molecules at length about 19 to 24 nucleotides, have established their value into multiple pathological processes, including cell proliferation, cell apoptosis and cell differentiation, through the post-transcriptional regulation of genes expression (6)(7)(8). Accumulating evidences disclose that several miRNAs act as important biomarkers for the diagnosis and prognosis of various cancers, such as NSCLC, pancreatic cancer and colorectal cancer (9)(10)(11).…”

microRNAs: Key players in virus‐associated hepatocellular carcinoma

“…Several studies have revealed an important role of miRNAs in HCC pathogenesis (Braconi, Henry, Kogure, Schmittgen, & Patel, ; Morishita & Masaki, ). miRNA enable to regulate a variety of targets involved in cancer via controlling a single gene (B. Zhang, Pan, Cobb, & Anderson, ) or through controlling multiple gene targets simultaneously (Damania et al, ; Y. Fang, Xue, Shen, Chen, & Tian, ; Fornari et al, ; Fu et al, ; Furuta et al, ; Garofalo et al, ; Y. Guo, Chen, Sun, & Yu, ; X. Jiang et al, ; F. F. Lan et al, ; W. Li, Dai, Ou, Zuo, & Liu, ; Y. Li et al, , ; F. Lin et al, ; K. Liu et al, ; Shan et al, ; Shimizu et al, ; Shiu et al, ; K. Tu, Liu, Yao, Han, & Yang, ; L. Wang, Yao, et al, ; W. Wang, Zhang, et al, ; Wong et al, ; F. Xie et al, ; G. Xu et al, ; J. Xu, Zhu, et al, ; T. Xu et al, ; Y. Xu, Huang, et al, ; Yan, Chen, Li, Wang, & Fan, ; Yuan et al, ; B. Zhang et al, ; S. Zhang, Shan, et al, ; Y. Zhang, Wei, et al, ; Figure ). miRNA networks are able to target one specific gene for fine‐tuning the expression of a specific protein in HCC cells (Buurman et al, ; Datta et al, ; S. Li et al, ; Shimizu et al, ; B. Zhang et al, ) or, alternatively, silencing a specific cellular and molecular pathway (W. Li et al, ; S. Tan, Li, Ding, Lobie, & Zhu, ; J. Xu et al, ; S. Zhang, Shan, et al, ).…”