Over-Expressed miR-224 Promotes the Progression of Cervical Cancer via Targeting RASSF8.
Cervical cancer is the most common cause of cancer-related deaths in women from developing countries. Identification of novel prognostic predictors or therapeutic targets may improve patient prognosis. In the current study, we demonstrated by real-time PCR that miR-224 expression was significantly upregulated (1.82-fold, P = 0.0025) in cervical cancer tissues (n = 126) compared with in normal cervical tissues (n = 64). Higher expression of miR-224 was significantly associated with poorer prognostic factors, including advanced FIGO stage, nodal metastasis, larger tumor size, vascular involvement and deep stromal invasion (all P < 0.05). Enforced expression of miR-224 promoted cell proliferation, migration and invasion in SiHa and CaSki cancer cell lines. Bioinformatic analysis indicated that RASSF8 (RAS-association domain family 8) was a potential target of miR-224. Western blot analysis and luciferase reporter assay showed that overexpressed miR-224 inhibited RASSF8 protein expression and decreased the activity of a luciferase reporter containing the 3' untranslated region (UTR) of RASSF8, respectively. Further, RASSF8 knockdown by specific RNAi showed similar effects in cervical cancer cells transfected with miR-224 mimic. Our findings suggest that miR-224 directly targets RASSF8 and thereby acts as a tumor promoter in cervical cancer progression.
Women's Reproductive Health Laboratory of Zhejiang Province, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
YongJie
Y
Huang
Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Yang
Y
Li
Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Fen F
FF
Wang
Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
WeiGuo
W
Lv
Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Xing
X
Xie
Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Xiaodong
X
Cheng
D000328:Adult; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000473:pathology*
C546140:MIRN224 microRNA, human; D035683:MicroRNAs; C512680:RASSF8 protein, human; D025521:Tumor Suppressor Proteins