MicroRNA-140-5p targets insulin like growth factor 2 mRNA binding protein 1 (IGF2BP1) to suppress cervical cancer growth and metastasis

• Published in: Oncotarget Vol. 7; no. 42; pp. 68397 - 68411
• Main Authors: Su, Yanlin, Xiong, Jie, Hu, Jinyue, Wei, Xin, Zhang, Xuelian, Rao, Lijuan
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 18.10.2016
• Subjects: 3' Untranslated Regions - genetics; Animals; Cell Line, Tumor; Cell Movement - genetics; Cell Proliferation - genetics; Female; Gene Expression Regulation, Neoplastic; HeLa Cells; Humans; Mice, Inbred BALB C; Mice, Nude; MicroRNAs - genetics; Neoplasm Metastasis; Research Paper; RNA Interference; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; Transplantation, Heterologous; Uterine Cervical Neoplasms - genetics; Uterine Cervical Neoplasms - metabolism; Uterine Cervical Neoplasms - pathology; IGF2BP1; tumor suppressor; cervical cancer; microRNA-140-5p
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.11722

MicroRNAs (miRNAs) are a class of small non-coding RNA molecules that play important roles in carcinogenesis and tumor progression. Previous studies have revealed that MicroRNA-140-5p (miR-140-5p) was abnormally expressed in several cancers. However, its function and possible mechanism in cervical cancer (CC) remains unknown. In this study, the data mining results showed that miR-140-5p was down-regulated in CC specimens and the down-regulation of miR-140-5p was associated with CC poor prognosis. These observations prompted us to further investigate the roles and mechanisms of miR-140-5p in human CC pathogenesis. We found that the over-expression/inhibition of miR-140-5p significantly decreased/increased cell proliferation, migration, and invasion in CC cells in vitro. Meanwhile, the results from in vivo assays showed that the over-expression of miR-140-5p induced significantly suppression of tumor growth and metastasis in nude mice. Furthermore, Insulin like growth factor 2 mRNA binding protein 1 (IGF2BP1) was identified as a direct target of miR-140-5p, and both gain-of-function and loss-of-function assays revealed that IGF2BP1 is also a functional target of miR-140-5p. Taken together, our findings suggested a novel miR-140-5p-IGF2BP1 regulatory circuit for CC pathogenesis, and miR-140-5p may be a potential target for CC therapy.