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MicroRNA195 inhibits cell proliferation, migration and invasion by targeting defective in cullin neddylation 1 domain containing 1 in cervical cancer

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MicroRNAs (miRs), a class of small noncoding RNAs, have been demonstrated to perform promoting or suppressive roles in various types of human malignancy. Deregulation of miR195 has been observed in numerous types of human cancer, including cervical cancer; however, the detailed molecular mechanism of miR195 underlying the malignant progression of cervical cancer remains largely unclear. In the present study, miR195 was significantly downregulated in cervical cancer tissue samples compared with adjacent nontumor tissue samples, and the reduced expression level of miR195 was associated with node metastasis and an advanced clinical stage in cervical cancer. Furthermore, the patients with low miR195 expression levels demonstrated shorter survival times when compared with those with high miR195 expression levels. In vitro experiments indicated that miR195 exerted suppressive effects on the proliferation, migration and invasion of cervical cancer cells. Luciferase reporter gene assay identified defective in cullin neddylation 1 domain containing 1 (DCUN1D1) as a novel target gene of miR195 and the expression level of DCUN1D1 was identified to be negatively regulated by miR195 in cervical cancer cells. DCUN1D1 was significantly upregulated in cervical cancer, with a negative correlation to miR195 expression. Furthermore, upregulation of DCUN1D1 was associated with the malignant progression and poor prognosis of cervical cancer. DCUN1D1 overexpression attenuated the suppressive effects of miR195 on the malignant phenotypes of cervical cancer cells. Notably, the expression levels of miR195 were significantly lower in HeLa [human papilloma virus (HPV)18+] and SiHa (HPV16+) cells compared with those in C33A (HPV) cells, and knockdown of E6 using small interfering RNA significantly increased the miR195 expression while the DCUN1D1 expression level was reduced in HeLa and SiHa cells. Thus, these findings indicate that miR195 exerts a suppressive role in cervical cancer by targeting DCUN1D1. Therefore, miR195 may present as a potential therapeutic candidate for cervical cancer.
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Document Type: Research Article

Affiliations: Department of Gynecology, Affiliated Qingdao Hiser Hospital of Qingdao University, Qingdao, Shandong 266000, P.R. China

Publication date: January 1, 2018

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  • The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.

    The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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