Abstract
BackgroundIncreasing evidence suggests that microRNAs (miRNAs) play critical roles in malignant transformation, tumor progression and metastasis. Aberrant miR-655-3p expression has been associated with several cancers. However, the role and underlying mechanism of miR-655-3p in the development of hepatocellular carcinoma (HCC) remains unclear.MethodsMiR-655-3p expression was detected by quantitative RT-PCR (qRT-PCR) in human HCC tissues and cell lines. Cell proliferation was investigated using MTT and colony formation assays, and cell migration and invasion abilities were evaluated by transwell assay. ADAM10 protein expression was detected by immunohistochemical assay. The target gene and downstream of miR-655-3p were determined by qRT-PCR, western blot and dual-luciferase reporter assays.ResultsmiR-655-3p was significantly down-regulated in HCC tissues and HCC cell lines. Low miR-655-3p expression was negatively related to tumor size, portal vein tumor thrombosis (PVTT) status, TNM stage and metastasis status. In addition, miR-655-3p overexpression and depletion decreased and increased HCC cell proliferation, migration and invasion, respectively. Moreover, ADAM10 was identified as a direct target of miR-655-3p, and miR-655-3p down-regulated E-cadherin protein level and inhibits β-catenin pathway by mediating ADAM10.ConclusionsMiR-655-3p might functions as a tumor suppressor by directly targeting ADAM10 and indirectly regulating β-catenin pathway in the development of progression of HCC. It may be a novel therapeutic candidate target to in HCC treatment.
Highlights
Increasing evidence suggests that microRNAs play critical roles in malignant transformation, tumor progression and metastasis
Previous study has demonstrated that miR-655inhibits epithelial mesenchymal transition (EMT) suppressive miRNA by targeting regulate ZEB1 and TGFBR2 inducing inactivation of the TGF-β signaling pathway [15]
Loss-of function of A disintegrin and metalloproteinase 10 (ADAM10) mimicked impact of miR-655-3p on hepatocellular carcinoma (HCC) cell proliferation and metastasis To confirm whether miR-655-3p dependent repression of HCC cell biological behaviors was mediated by ADAM10, we investigated the expression and role of ADAM10 in HCC
Summary
Increasing evidence suggests that microRNAs (miRNAs) play critical roles in malignant transformation, tumor progression and metastasis. Wu et al Journal of Experimental & Clinical Cancer Research (2016) 35:89 ample miRNAs can function as tumor suppressors or oncogenes to play important roles in the initiation, promotion and progression of various cancers [7], and aberrant miRNAs expression might be of potential use as a diagnostic and prognostic biomarker for human cancer including HCC. MiRNAs on this locus have been reported associated with a metastatic phenotype in clinical cancer samples [12], and ectopic expression of 14q32-encoded microRNAs can reduce cell-autonomous metastatic properties in vitro and inhibit metastasis development in vivo [13]. MiR-655-3p expression is reduced in several cancers and overexpression of miR-655 act as a tumor suppressor by targeting pituitary tumor-transforming gene-1(PTTG1) in esophageal squamous cell carcinoma metastasis [14]. The expression level of miR-655-3p and its roles in the development of HCC have not yet been reported
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