title: The correlation between microRNA490-3p and TGFα in endometrial carcinoma tumorigenesis and progression.
abstract: MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate the translation of messenger RNAs by binding their 3'-untranslated region (3' UTR). MiR-490-3p has been reported to be a suppressor in various human cancers; however, little is known about the biological functions of miR-490-3p in endometrial cancer (EC). In our study, we found that MiR-490-3p mRNA expression was significantly lower in ECs than in normal endometrial tissues. MiR-490-3p mRNA expression was also negatively associated with depth of invasion (mucosa vs. muscular and serosa) and lymph node metastasis (negative vs. positive) in EC. MiR-490-3p overexpression reduced proliferation; promoted G1 arrest and apoptosis; suppressed migration and invasion; and reduced TGFα, NF-kB, cyclin D1, survivin, matrix metalloproteinase 2 (MMP2) mRNA and protein expression, and improved Bax mRNA and protein expression. The dual-luciferase reporter assay indicated that miR-490-3p directly targeted TGFα by binding its 3' untranslated region. MiR-490-3P transfection also suppressed tumor development and TGFα expression (as determined by immunohistochemistry and western blotting) in vivo in the xenograft mouse model. This is the first demonstration that miR-490-3P might act as a suppressor in EC tumorigenesis and progression by targeting TGFα. Our results provide a theoretical basis for the further study on the molecular target for endometrial cancer.
authors: Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang, P.R. China.
authors: Kai-Xuan
authors: KX
authors: Sun
authors: Department of Gynecology, The Fourth Affiliated Hospital of China Medical University, Shenyang, P.R. China.
authors: Ying
authors: Y
authors: Chen
authors: Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang, P.R. China.
authors: Shuo
authors: S
authors: Chen
authors: Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang, P.R. China.
authors: Bo-Liang
authors: BL
authors: Liu
authors: Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang, P.R. China.
authors: Miao-Xiao
authors: MX
authors: Feng
authors: Department of Biochemistry and Molecular Biology, College of Basic Medicine, China Medical University, Shenyang, P.R. China.
authors: Zhi-Hong
authors: ZH
authors: Zong
authors: Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang, P.R. China.
authors: Yang
authors: Y
authors: Zhao
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000368:Aged; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D016889:Endometrial Neoplasms / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000235:genetics; D009368:Neoplasm Transplantation; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis; D034741:RNA, Small Interfering / Q000235:genetics; D000077022:Survivin; D016211:Transforming Growth Factor alpha / Q000235:genetics* / Q000378:metabolism; D014183:Transplantation, Heterologous; D014599:Uterus / Q000473:pathology
chemical_list: D020413:3' Untranslated Regions; C107489:BIRC5 protein, human; C530104:CCND1 protein, human; D051034:Inhibitor of Apoptosis Proteins; C574862:MIRN490 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D000077022:Survivin; D016211:Transforming Growth Factor alpha; D019938:Cyclin D1; C512478:EGFR protein, human; D066246:ErbB Receptors; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2
keywords: TGFα; carcinogenesis; endometrial carcinoma; metastasis; microRNA