RUNX2 promotes hepatocellular carcinoma cell migration and invasion by upregulating MMP9 expression.
Runt-related transcription factor 2 (RUNX2) was first identified as a transcription factor to play an important role in different biological processes of osteoblast and chondrocyte, including differentiation and migration. Recently, RUNX2 has been implicated in promigratory/proinvasive behavior in different human malignancies. In the present study, we demonstrated that the RUNX2 mRNA and protein expression were both increased significantly in HCC tissues and cell lines. High RUNX2 expression was correlated obviously with poor clinicopathological characteristics including multiple tumor nodes, high histological grading, venous infiltration and advanced tumor-node-metastasis (TNM) stage. In addition, we demonstrated that RUNX2 was a prognostic indicator for predicting 5-year overall survival and disease-free survival of HCC patients. Our studies showed that RUXN2 overexpression promoted, while RUNX2 knockdown inhibited HCC cell migration and invasion in vitro. Notably, RUNX2 positively regulated matrix metalloproteinase 9 (MMP9) accumulation in HCC cells. Furthermore, we confirmed that RUNX2 was positively correlated with MMP9 expression in HCC tissues by Pearson correlation analysis. Mechanistically, we demonstrated that MMP9 overexpression increased HCC cell migration and invasion, while MMP9 knockdown reduced HCC cell migration and invasion in vitro. Alteration of MMP9 expression partially abrogated the effects of RUNX2 on HCC cell migration and invasion, which suggests that RUNX2 developed its pro-metastatic biological function by upregulating the expression of MMP9 in HCC cells. In conclusion, our results reveal that RUNX2 promotes HCC cell migration and invasion by MMP9-mediated pathway, and potentially serves as a new prognostic biomarker and in therapeutic strategies for HCC.
Department of Hepato-biliary-pancreatic surgery, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan 450000, P.R. China.
Qian
Q
Wang
Department of Hepato-biliary-pancreatic surgery, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan 450000, P.R. China.
Wei
W
Yu
Department of Hepato-biliary-pancreatic surgery, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan 450000, P.R. China.
Tao
T
Huang
Department of Medical Oncology, People's Hospital of Henan Province, Zhengzhou, Henan 450000, P.R. China.
Yan
Y
Zhu
Department of Hepato-biliary-pancreatic surgery, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan 450000, P.R. China.
Changshan
C
Huang
D000328:Adult; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D002465:Cell Movement / Q000235:genetics; D050659:Core Binding Factor Alpha 1 Subunit / Q000096:biosynthesis* / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D015398:Signal Transduction
D014408:Biomarkers, Tumor; D050659:Core Binding Factor Alpha 1 Subunit; C493709:RUNX2 protein, human; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9