Micro ribonucleic acid-93 promotes oncogenesis of cervical cancer by targeting RAB11 family interacting protein 1.
OBJECTIVE
Micro ribonucleic acid (RNA)-93 (miR-93) is a novel oncogenic miRNA dysregulated in many types of tumors. We aimed to further study the expression pattern and clinical significance of miR-93 and its target, the RAB11 family interacting protein 1 (RAB11FIP1) gene, in cervical cancer.


METHODS
Mir-93 and RAB11FIP1 expression in cervical cancer (n = 168), cervical intraepithelial neoplasia (CIN) 2 or 3 (n = 60) and normal cervical tissues (n = 48) was examined by real-time reverse transcription polymerase chain reaction and immunohistochemical staining. Methyl thiazolyl tetrazolium assay, flow cytometry, and Transwell chamber invasion assay were performed to investigate the function of miR-93 in the proliferation, apoptosis and invasion of cervical cancer cell lines SiHa and CaSki. Luciferase activity assay was conducted to identify the target gene of miR-93.


RESULTS
Mir-93 expression levels in cervical cancer and CIN tissues were significantly increased (P = 0.032), but the RAB11FIP1 protein was significantly decreased (P = 0.006) compared with normal tissues. Neither was associated with clinicopathological variables. Enforced miR-93 knockdown or RAB11FIP1 overexpression suppressed proliferation and promoted apoptosis, but did not influence invasion in cervical cancer cells. Luciferase activity indicated that RAB11FIP1 was a direct target for miR-93.


CONCLUSIONS
Our findings suggest that overexpression of miR-93 via targeting RAB11FIP1 as an early event plays an important role in oncogenesis of cervical cancer. MiR-93 and its target protein RAB11FIP1 may be potential therapeutic targets for cervical cancer and its precursors.
Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Jing
J
Zhang
Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Fenfen
F
Wang
Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Junfen
J
Xu
Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Xinyu
X
Wang
Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Feng
F
Ye
Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China. xingxiee@163.com.
Xing
X
Xie
D020413:3' Untranslated Regions; D000328:Adult; D000368:Aged; D017209:Apoptosis; D063646:Carcinogenesis / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002584:Cervix Uteri / Q000378:metabolism; D005260:Female; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D002583:Uterine Cervical Neoplasms / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000378:metabolism*; D002578:Uterine Cervical Dysplasia / Q000378:metabolism*; D000099193:rab11 GTP-Binding Proteins
D020413:3' Untranslated Regions; D035683:MicroRNAs; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C543350:MIRN93 microRNA, human
RAB11FIP1; cervical cancer; miR-93; miRNA