title: miR-152 functions as a tumor suppressor in colorectal cancer by targeting PIK3R3.
abstract: Accumulating evidence showed that microRNA-152 (miR-152) was frequently downregulated, and functioned as tumor suppressor in many cancers, but little is known about its biological role and intrinsic regulatory mechanisms in colorectal cancer (CRC). Here, we explored the potential role of miR-152 in CRC and the possible molecular mechanisms. Our results proved that miR-152 expression was downregulated in CRC cell lines and tissue samples, and its expression was inversely correlated with advanced tumor-node-metastasis (TNM) stage (P < 0.01) and lymph node metastasis (P < 0.01). Function assays demonstrated that restoring the expression of miR-152 in CRC cells dramatically reduced the cell proliferation and cell migration and invasion and promoted apoptosis and caspase-3 activity in vitro, as well as suppressed tumor growth in vivo. Mechanistic investigations defined phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3) as a direct and functional downstream target of miR-152. In addition, we also found that PIK3R3 expression was upregulated and was inversely correlated with miR-152 expression in clinical CRC tissues. Downregulation of PIK3R3 mimicked the tumor-suppressive effects of miR-152 overexpression in CRC cells. Taken together, these results elucidated the function of miR-152 in CRC progression and suggested that miR-152 might function as tumor suppressor in CRC by targeting PIK3R3.
authors.affiliation: Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, 130033, People's Republic of China.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, 130033, People's Republic of China.
authors.forename: Zhongshi
authors.initials: Z
authors.lastname: Xie
authors.affiliation: Department of Colorectal and Anal Surgery, the First Hospital of Jilin University, Changchun, 130021, People's Republic of China. libai1502@sina.com.
authors.forename: Bai
authors.initials: B
authors.lastname: Li
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000368:Aged; D000818:Animals; D017209:Apoptosis; D002455:Cell Division; D045744:Cell Line, Tumor; D002465:Cell Movement; D015179:Colorectal Neoplasms / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D016147:Genes, Tumor Suppressor; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D012313:RNA / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics*; D015398:Signal Transduction; D014162:Transfection; D014410:Tumor Stem Cell Assay
chemical_list: D020413:3' Untranslated Regions; C550856:MIRN152 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; C039919:RNA, recombinant; D012313:RNA; D019869:Phosphatidylinositol 3-Kinases; C523442:PIK3R3 protein, human
keywords: Colorectal cancer; MicroRNAs; PIK3R3; Tumor suppressor; miR-152
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