title: miR-96 promotes the growth of prostate carcinoma cells by suppressing MTSS1.
abstract: Prostate carcinoma (PC) is one of the most common cancers for males. However, the molecular mechanisms of PC progression are still to be uncovered. MicroRNA (miRNA) has been shown to be associated with the initiation and progression of prostate cancer. Among the identified tumor-promoting miRNAs, miR-96 has been well established to contribute to PC by reducing FOXO1 expression. This study is aimed to study if miR-96 can promote the progression of PC through other pathways. Our data reinforced the finding that the level of miR-96 was higher in PC samples and cell lines than in non-cancerous tissues and normal prostate epithelial cells. In addition, serum miR-96 abundance was also found to be elevated in PC patients. Decreasing miR-96 expression was able to suppress the proliferation, clonogenicity, and invasion of PC cells. Overexpressing miR-96 led to increased proliferation and colony formation of normal prostate epithelial cells. miR-96 level was found to be inversely associated with the abundance of metastasis suppressor protein 1 (MTSS1) messenger RNA (mRNA), which has been proved to be a tumor suppressor for PC. Predictive analysis indicated that there was a potential miRNA response elements (MREs) located within 3'UTR of MTSS1 mRNA. The changes in miR-96 expression can affect the levels of MTSS1 both at mRNA and protein levels. miR-96 also suppressed the activity of luciferase reporter under the regulation of 3'UTR of MTSS1. Further studies showed that MTSS1 restoration accounted for the effect of miR-96 reduction on PC cells. The overexpression of a recombinant MTSS1 resistant against miRNA regulation was also demonstrated to abolish the transforming effect of miR-96 on prostate epithelial cells. Taken together, we found that miR-96 has a higher abundance in serum samples of PC patients than healthy controls, implying that it may be used as a prognostic marker. MTSS1 is a new authentic target of miR-96 in PC. The above findings suggested that targeting miR-96 may be a promising strategy for PC treatment.
authors.affiliation: Department of Pathophysiology, College of Basic Medicine Sciences, Jilin University, Xinmin Street, Changchun, 130021, China.
authors.forename: Libo
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Pathology, School of Basic Medicine Sciences, Xinxiang Medical University, Xinxiang, China.
authors.forename: Jiateng
authors.initials: J
authors.lastname: Zhong
authors.affiliation: Department of Plastic Surgery, The China-Japan Union Hospital, Jilin University, Changchun, China.
authors.forename: Baofeng
authors.initials: B
authors.lastname: Guo
authors.affiliation: Department of Pathophysiology, College of Basic Medicine Sciences, Jilin University, Xinmin Street, Changchun, 130021, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: Department of Pathophysiology, College of Basic Medicine Sciences, Jilin University, Xinmin Street, Changchun, 130021, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Liang
authors.affiliation: Department of Pathophysiology, College of Basic Medicine Sciences, Jilin University, Xinmin Street, Changchun, 130021, China.
authors.forename: Naiyan
authors.initials: N
authors.lastname: Wen
authors.affiliation: Department of Pathophysiology, College of Basic Medicine Sciences, Jilin University, Xinmin Street, Changchun, 130021, China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Yun
authors.affiliation: Department of Pathophysiology, College of Basic Medicine Sciences, Jilin University, Xinmin Street, Changchun, 130021, China. zhangling3@jlu.edu.cn.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000502:physiology*; D008840:Microfilament Proteins / Q000032:analysis / Q000235:genetics*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: C541492:MIRN96 microRNA, human; C486778:MTSS1 protein, human; D035683:MicroRNAs; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins
keywords: Growth; MTSS1; Proliferation; Prostate carcinoma; miR-96