title: MACC1 induces metastasis in ovarian carcinoma by upregulating hepatocyte growth factor receptor c-MET.
abstract: Metastasis-associated in colon cancer 1 (MACC1) is a newly identified gene that has been shown to promote tumor cell invasion and metastasis. The present study investigated the effect of MACC1 downregulation on the biological characteristics of the ovarian cancer OVCAR3 cell line. In this study, MACC1 expression was blocked using the RNA interference technique. The downregulation of MACC1 mRNA and protein expression was confirmed using quantitative polymerase chain reaction and western blot analysis. The proliferative activity and adhesion rate of the cells were detected using cell counting kit-8 and a cell adhesion assay, while cell invasion was determined using a Matrigel invasion assay and migration capacity was observed using migration and wound-healing assays. A tube formation assay was also used to examine the angiogenic capacity of cells, and a luciferase assay was performed to assess whether MACC1 binds to the c-MET gene. The MACC1 mRNA and protein expression levels were significantly downregulated using sequence-specific small interfering RNA (siRNA). The inhibition of MACC1 expression markedly decreased the invasive, metastatic and angiogenic capacities of the cells, but only slightly inhibited growth and adhesion. In addition, a putative MACC1-binding site was identified in the 3'-untranslated region of c-MET. MACC1-siRNA was also found to significantly reduce the expression of the c-MET protein and a luciferase reporter assay confirmed that c-MET was the target gene of MACC1. These results demonstrated that the attenuation of MACC1 suppresses cell invasion and migration and that MACC1 may regulate cell metastasis through targeting the expression of c-MET. Inhibition of the function of MACC1 may represent a new strategy for treating ovarian cancer.
authors.affiliation: Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510150, P.R. China.
authors.forename: Xiu-Jie
authors.initials: XJ
authors.lastname: Sheng
authors.affiliation: Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510150, P.R. China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510150, P.R. China.
authors.forename: Man
authors.initials: M
authors.lastname: Sun
authors.affiliation: Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510150, P.R. China.
authors.forename: Zhi-Hui
authors.initials: ZH
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510150, P.R. China.
authors.forename: Dong-Mei
authors.initials: DM
authors.lastname: Zhou
authors.affiliation: Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510150, P.R. China.
authors.forename: Jian-Qi
authors.initials: JQ
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510150, P.R. China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, Guangzhou, Guangdong 510150, P.R. China.
authors.forename: Xiao-Fang
authors.initials: XF
authors.lastname: Sun
authors.affiliation: Experimental Medical Research Center of Guangzhou Medical University, Guangzhou, Guangdong 510182, P.R. China.
authors.forename: Qi-Cai
authors.initials: QC
authors.lastname: Liu
keywords: c-MET; metastasis; metastasis-associated in colon cancer 1; ovarian carcinoma