Knockdown of RHOC by shRNA suppresses invasion and migration of cholangiocellular carcinoma cells via inhibition of MMP2, MMP3, MMP9 and epithelial-mesenchymal transition.
Ras homolog family member C (RHOC) is important during the progression of several types of cancer, including prostate, breast and hepatocellular carcinoma. However, the function of RHOC in cholangiocellular carcinoma (CCC), a highly recurrent and metastatic carcinoma with poor prognosis, remains unclear. The aim of the present study was to investigate the involvement of RHOC in CCC tumor progression. RHOC expression levels were examined in CCC tissues and cells, and adjacent nontumorous bile duct tissues. The effects and molecular mechanisms of RHOC expression on cell migration and invasion were also investigated. The current study demonstrated that RHOC protein was frequently overexpressed in human CCC specimens and CCC cell lines. Downregulation of RHOC inhibited CCC cell invasion and migration partially via inhibition of matrix metalloproteinase 2, 3 and 9 expression. RHOC also modulated the expression of several epithelial-mesenchymal transition (EMT)-associated proteins, including E‑cadherin, vimentin, Slug and Snail, to promote to EMT progression. The present results demonstrated that RHOC is important for the invasion and migration of CCC through simultaneous regulation of MMPs and EMT‑associated protein, suggesting that RHOC is a potential molecular target for CCC treatment.
Department of Radiotherapy, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China.
Haixia
H
Yang
Department of Radiotherapy, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China.
Jun
J
Liang
Department of Medical Oncology, Xi'an Chest Hospital of Shaanxi, Xi'an, Shaanxi 710061, P.R. China.
Jiupeng
J
Zhou
Department of Pathology, First Affiliated Hospital of Henan Science and Technology University, Luoyang, Henan 471003, P.R. China.
Jianqiang
J
Mi
Department of Medical Oncology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710062, P.R. China.
Ke
K
Ma
Department of Medical Oncology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710062, P.R. China.
Yangwei
Y
Fan
Department of Medical Oncology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710062, P.R. China.
Jing
J
Ning
Department of Medical Oncology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710062, P.R. China.
Chuying
C
Wang
Department of Medical Oncology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710062, P.R. China.
Xin
X
Wei
Department of Medical Oncology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710062, P.R. China.
Enxiao
E
Li
D001650:Bile Duct Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D018281:Cholangiocarcinoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis* / Q000235:genetics; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis* / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000235:genetics; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D034741:RNA, Small Interfering; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D000075024:rhoC GTP-Binding Protein
D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; C066690:RHOC protein, human; D020741:rho GTP-Binding Proteins; D000075024:rhoC GTP-Binding Protein