title: MiR-145 is downregulated in human ovarian cancer and modulates cell growth and invasion by targeting p70S6K1 and MUC1.
abstract: MicroRNAs (miRNAs) are a family of small non-coding RNA molecules that regulate gene expression at post-transcriptional levels. Previous studies have shown that miR-145 is downregulated in human ovarian cancer; however, the roles of miR-145 in ovarian cancer growth and invasion have not been fully demonstrated. In the present study, Northern blot and qRT-PCR analysis indicate that miR-145 is downregulated in ovarian cancer tissues and cell lines, as well as in serum samples of ovarian cancer, compared to healthy ovarian tissues, cell lines and serum samples. Functional studies suggest that miR-145 overexpression leads to the inhibition of colony formation, cell proliferation, cell growth viability and invasion, and the induction of cell apoptosis. In accordance with the effect of miR-145 on cell growth, miR-145 suppresses tumor growth in vivo. MiR-145 is found to negatively regulate P70S6K1 and MUC1 protein levels by directly targeting their 3'UTRs. Importantly, the overexpression of p70S6K1 and MUC1 can restore the cell colony formation and invasion abilities that are reduced by miR-145, respectively. MiR-145 expression is increased after 5-aza-CdR treatment, and 5-aza-CdR treatment results in the same phenotype as the effect of miR-145 overexpression. Our study suggests that miR-145 modulates ovarian cancer growth and invasion by suppressing p70S6K1 and MUC1, functioning as a tumor suppressor. Moreover, our data imply that miR-145 has potential as a miRNA-based therapeutic target for ovarian cancer.
authors.affiliation: Department of Gynecological Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
authors.forename: Huijuan
authors.initials: H
authors.lastname: Wu
authors.forename: Zhenghua
authors.initials: Z
authors.lastname: Xiao
authors.forename: Ke
authors.initials: K
authors.lastname: Wang
authors.forename: Wenxin
authors.initials: W
authors.lastname: Liu
authors.forename: Quan
authors.initials: Q
authors.lastname: Hao
mesh_terms: D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000097:blood / Q000235:genetics / Q000502:physiology*; D018396:Mucin-1 / Q000096:biosynthesis* / Q000235:genetics; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology*; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C541010:MIRN145 microRNA, human; C060192:MUC1 protein, human; D035683:MicroRNAs; D018396:Mucin-1; D038762:Ribosomal Protein S6 Kinases, 70-kDa
keywords: MUC1; Ovarian cancer; miR-145; p70S6K1