title: MiR-195 inhibits the proliferation of human cervical cancer cells by directly targeting cyclin D1.
abstract: MicroRNAs are important regulators of multiple cellular processes, and aberrant miRNA expression has been observed in human cervical cancer (CC). The present study was to evaluate the level of miR-195 and cyclin D1 in CC tissues and cells. We further investigated the molecular mechanisms of miR-195 and cyclin D1 in CC cell lines HeLa and SiHa. Here, we found that miR-195 expression was down-regulated in CC tissues, and HeLa and SiHa cells (all p < 0.001). By contrast, cyclin D1 was up-regulated. Furthermore, the expression of miR-195 was inversely proportional to that of cyclin D1 mRNA or protein (p = 0.013, p = 0.015, respectively). In vitro studies demonstrated that the overexpression of miR-195 played a suppressor role in the proliferation of HeLa and SiHa cells and promoted cell apoptosis. Luciferase reporter assays confirmed that miR-195 binding to the 3'-UTR regions of cyclin D1 inhibited the expression of cyclin D1 in HeLa and SiHa cells. However, the inhibitor of miR-195 promoted the expression of cyclin D1 and cell proliferation. In conclusion, our data suggest that miR-195 may have the potential role in treatment of CC patients, as well as miR-195 is a novel regulator of invasiveness and tumorigenicity in CC cells by targeting cyclin D1. MiR-195/cyclin D1 pathway may be a useful therapeutic agent in CC patients.
authors.affiliation: Department of Gynecological Oncology, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Wuhan, 430071, Hubei, People's Republic of China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynecology, Xiangyang First People's Hospital, Affiliated Hospital of Hubei University of Medicine, Xiangyang, 441100, Hubei, People's Republic of China.
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Gynecological Oncology, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Wuhan, 430071, Hubei, People's Republic of China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Gynecological Oncology, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Wuhan, 430071, Hubei, People's Republic of China. caihbwuhan@163.com.
authors.forename: Hongbing
authors.initials: H
authors.lastname: Cai
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D034622:RNA Interference; D002583:Uterine Cervical Neoplasms / Q000235:genetics*; D055815:Young Adult
chemical_list: D020413:3' Untranslated Regions; C552722:MIRN195 microRNA, human; D035683:MicroRNAs; D019938:Cyclin D1
keywords: Cervical cancer; Cyclin D1; MiR-195