MicroRNA-655-3p functions as a tumor suppressor by regulating ADAM10 and β-catenin pathway in Hepatocellular Carcinoma.
Increasing 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.



MiR-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.



miR-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.



MiR-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.
Department of General Surgery, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China. wgzwl@hotmail.com.
Gang
G
Wu
Department of General Surgery, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China.
Kunming
K
Zheng
Department of Breast and Thyroid Surgery, Huaihe Hospital, Henan University, Kaifeng, 475000, China.
Shuguan
S
Xia
Department of General Surgery, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China.
Yawei
Y
Wang
Department of Gastric Surgery, Liaoning Cancer Hospital and Institute, Shenyang, 110001, China.
Xiangyu
X
Meng
Department of General Surgery, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China.
Xiaoming
X
Qin
Department of General Surgery, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China.
Ying
Y
Cheng
D020413:3' Untranslated Regions; D000072197:ADAM10 Protein / Q000235:genetics*; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D015398:Signal Transduction; D051176:beta Catenin / Q000235:genetics*
D020413:3' Untranslated Regions; C495270:CTNNB1 protein, human; C585264:MIRN655 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; D051176:beta Catenin; D053829:Amyloid Precursor Protein Secretases; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human
ADAM10; Hepatocellular carcinoma; Migration and invasion; Proliferation; miR-655-3p; β-catenin pathway