title: The role of metastasis-associated in colon cancer 1 (MACC1) in endometrial carcinoma tumorigenesis and progression.
abstract: Metastasis-associated in colon cancer-1 (MACC1), has recently been identified as a key regulator in the progression of many cancers. However, its role in endometrial carcinoma (EC) remains unknown. MACC1 expression was determined in EC and normal endometrial tissues by immunohistochemistry. EC cell phenotypes and related molecules were examined after MACC1 downregulation by Small interfering RNA (siRNA) or microRNA (miRNA) transfection. We found that MACC1 was highly expressed in EC tissues than normal samples, and was significantly different in FIGO staging (I and II vs. III and IV), the depth of myometrial infiltration (<1/2 vs. ≥1/2), lymph nodes metastasis (negative vs. positive), besides, MACC1 overexpression was correlated with lower cumulative and relapse-free survival rate. MACC1 downregulation by siRNA transfection significantly induced G1 phrase arrest, suppressed EC cell proliferation, migration, and invasion. In addition, MACC1 downregulation also reduced expression of Cyclin D1 and Cyclin-dependent Kinase 2 (CDK2), N-cadherin (N-Ca), α-SMA, matrix metalloproteinase 2 (MMP2), and MMP9, but increased expression of E-cadherin (E-Ca). Bioinformatic predictions and dual-luciferase reporter assays indicate that MACC1 is a possible target of miR-23b. MiR-23b overexpression reduced MACC1 expression in vitro and induced G1 phrase arrest, suppressed cell proliferation, migration, and invasion. MiR-23b transfection also reduced Cyclin D1 and CDK2, N-Ca, α-SMA, MMP2, MMP9 expression, but increased E-Ca expression. Furthermore, the nude mouse xenograft assay showed that miR-23b overexpression suppressed tumour growth through downregulating MACC1 expression. Taken together, our results demonstrate for the first time that MACC1 may be a new and important diagnosis and therapeutic target of endometrial carcinoma.
authors.affiliation: Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang, China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Basic Medicine, China Medical University, Shenyang, China.
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Zong
authors.affiliation: Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang, China.
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Wu
authors.affiliation: Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang, China.
authors.forename: Kai-Xuan
authors.initials: KX
authors.lastname: Sun
authors.affiliation: Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang, China.
authors.forename: Bo-Liang
authors.initials: BL
authors.lastname: Liu
authors.affiliation: Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000235:genetics* / Q000473:pathology; D002465:Cell Movement; D049109:Cell Proliferation; D015536:Down-Regulation; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology; D004717:Endometrium / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C544162:MACC1 protein, human; C552430:MIRN23a microRNA, human; D035683:MicroRNAs; D015534:Trans-Activators; D014157:Transcription Factors
keywords: MACC1; endometrial carcinoma; epithelial-mesenchymal transition; progression; tumorigenesis