MicroRNA-373 functions as an oncogene and targets YOD1 gene in cervical cancer.
miR-373 was reported to be elevated in several tumors; however, the role of miR-373 in cervical cancer has not been investigated. In this study we aimed to investigate the role of miR-373 in tumorigenicity of cervical cancer cells in vivo and in vitro. The expression of miR-373 was investigated using real-time reverse transcription-polymerase chain reaction assay in 45 cervical specimens and cervical cancer cell lines. The role of miR-373 in tumorigenicity of cervical cancer cells was assessed by cell proliferation, colony formation in vitro as well as tumor growth assays in vivo with the overexpression of miR-373 or gene silencing. The functional target gene of miR-373 in cervical cancer cells was identified using integrated bioinformatics analysis, gene expression arrays, and luciferase assay. We founded that the expression of miR-373 is upregulated in human cervical cancer tissues and cervical carcinoma cell lines when compared to the corresponding noncancerous tissues. Ectopic overexpression of miR-373 in human cervical cancer cells promoted cell growth in vitro and tumorigenicity in vivo, whereas silencing the expression of miR-373 decreased the rate of cell growth. YOD1 was identified as a direct and functional target of miR-373 in cervical cancer cells. Expression levels of miR-373 were inversely correlated with YOD1 levels in human cervical cancer tissues. RNAi-mediated knockdown of YOD1 phenocopied the proliferation-promoting effect of miR-373. Moreover, overexpression of YOD1 abrogated miR-373-induced proliferation of cervical cancer cells. These results demonstrate that miR-373 increases proliferation by directly targeting YOD1, a new potential therapeutic target in cervical cancer.
Department of Obstetrics and Gynecology, RenJi Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai Key Laboratory of Gynecologic Oncology, Shanghai 200127, China.
Luo-Qiao
LQ
Wang
Department of Obstetrics and Gynecology, RenJi Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai Key Laboratory of Gynecologic Oncology, Shanghai 200127, China.
Yue
Y
Zhang
Department of Obstetrics and Gynecology, RenJi Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai Key Laboratory of Gynecologic Oncology, Shanghai 200127, China.
Huan
H
Yan
Department of Obstetrics and Gynecology, RenJi Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai Key Laboratory of Gynecologic Oncology, Shanghai 200127, China. Electronic address: liukaijiang@126.com.
Kai-Jiang
KJ
Liu
Department of Obstetrics and Gynecology, RenJi Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai Key Laboratory of Gynecologic Oncology, Shanghai 200127, China. Electronic address: drzhangshu@126.com.
Shu
S
Zhang
D020413:3' Untranslated Regions; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D010450:Endopeptidases / Q000235:genetics*; D005260:Female; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D064593:Heterografts; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D009368:Neoplasm Transplantation; D009857:Oncogenes; D013869:Thiolester Hydrolases / Q000037:antagonists & inhibitors / Q000235:genetics*; D014410:Tumor Stem Cell Assay; D015854:Up-Regulation; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology
D020413:3' Untranslated Regions; C527114:MIRN373 microRNA, human; D035683:MicroRNAs; C545663:YOD1 protein, human; D013869:Thiolester Hydrolases; D010450:Endopeptidases
Human cervical cancer; Tumorigenicity; YOD1; miR-373