title: Down-regulation of microRNA-135b inhibited growth of cervical cancer cells by targeting FOXO1.
abstract: More and more evidence has confirmed that dysregulation of microRNAs (miRNAs) can conduce to the progression of human cancers. Previous studied have shown that dysregulation of miR-135b is in varieties of tumors. However, the roles of miR-135b in cervical cancer remain unknown. Therefore, our aim of this study was to explore the biological function and molecular mechanism of miR-135b in cervical cancer cell lines, discussing whether it could be a therapeutic biomarker of cervical cancer in the future. The MTT assay and ELISA-Brdu assay were used to assess cell proliferation. Cell cycle was detected by flow cytometry. Real-time quantitative polymerase chain reaction (PCR) and Western blot analyses were used to detect expressions of cyclin D1, p21, p27 and FOXO1. In our study, we found that miR-135b is up-regulated in cervical cancer cell lines. Down-regulation of miR-135b evidently inhibited proliferation and arrested cell cycle in cervical cancer cells. Bioinformatics analysis predicted that the FOXO1 was a potential target gene of miR-135b. Besides, miR-135b inhibition significantly increased expressions of the cyclin-dependent kinase inhibitors, p21(/CIP1) and p27(/KIP1), and decreased expression of cyclin D1. However, the high level of miR-135b was associated with increased expression of FOXO1 in cervical cancer cells. Further study by luciferase reporter assay demonstrated that miR-135b could directly target FOXO1. Down-regulation of FOXO1 in cervical cancer cells transfected with miR-135b inhibitor partially reversed its inhibitory effects. In conclusion, down-regulation of miR-135b inhibited cell growth in cervical cancer cells by up-regulation of FOXO1.
authors.affiliation: Department of Obstetrics and Gynecology, The Eastern Division of The First Hospital of Jilin University Changchun 130031, People's Republic of China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Obstetrics and Gynecology, The Second Hospital of Jilin University Changchun 130041, People's Republic of China.
authors.forename: Shuhua
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Obstetrics and Gynecology, The Second Hospital of Jilin University Changchun 130041, People's Republic of China.
authors.forename: Manhua
authors.initials: M
authors.lastname: Cui
authors.affiliation: Department of Obstetrics and Gynecology, The Second Hospital of Jilin University Changchun 130041, People's Republic of China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
mesh_terms: D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D015536:Down-Regulation; D005260:Female; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C544965:MIRN135 microRNA, human; D035683:MicroRNAs
keywords: Cervical cancer; FOXO1; cell cycle; miR-135b; proliferation