title: Role of microRNA 30a targeting insulin receptor substrate 2 in colorectal tumorigenesis.
abstract: MicroRNAs (miRNAs) are dysregulated in many types of malignant diseases, including colorectal cancer. miRNA 30a (miR-30a) is a member of the miR-30 family and has been implicated in many types of cancers. In this study, we determined the expression of miR-30a in human colon cancer tissues and cell lines. miR-30a was found to be significantly downregulated in both the tissues and cell lines. Furthermore, overexpression of miR-30a inhibited, while silencing of miR-30a promoted, cell proliferation, migration, and invasion in vitro. Consistently, stable overexpression of miR-30a suppressed the growth of colon cancer cell xenografts in vivo. Moreover, bioinformatic algorithms and luciferase reporter assays revealed that insulin receptor substrate 2 (IRS2) is a direct target of miR-30a. Further functional studies suggested that repression of IRS2 by miR-30a partially mediated the tumor suppressor effect of miR-30a. In addition, miR-30a inhibited constitutive phosphorylation of Akt by targeting IRS2. Additionally, clinicopathological analysis indicated that miR-30a has an inverse correlation with the staging in patients with colon cancer. Taken together, our study provides the first evidence that miR-30a suppressed colon cancer cell growth through inhibition of IRS2. Thus, miR-30a might serve as a promising therapeutic strategy for colon cancer treatment.
authors.affiliation: Department of Colorectal Cancer Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People's Republic of China Colorectal Cancer Institute of Harbin Medical University, Harbin, Heilongjiang, People's Republic of China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Colorectal Cancer Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People's Republic of China Colorectal Cancer Institute of Harbin Medical University, Harbin, Heilongjiang, People's Republic of China.
authors.forename: Qingchao
authors.initials: Q
authors.lastname: Tang
authors.affiliation: Department of Nephrology, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People's Republic of China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Qin
authors.affiliation: Department of Colorectal Cancer Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People's Republic of China Colorectal Cancer Institute of Harbin Medical University, Harbin, Heilongjiang, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Colorectal Cancer Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People's Republic of China Colorectal Cancer Institute of Harbin Medical University, Harbin, Heilongjiang, People's Republic of China.
authors.forename: Rui
authors.initials: R
authors.lastname: Huang
authors.affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.
authors.forename: Guixiang
authors.initials: G
authors.lastname: Lv
authors.affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Zou
authors.affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.
authors.forename: Xiao-chen
authors.initials: XC
authors.lastname: Jiang
authors.affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.
authors.forename: Chendan
authors.initials: C
authors.lastname: Zou
authors.affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Colorectal Cancer Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People's Republic of China Colorectal Cancer Institute of Harbin Medical University, Harbin, Heilongjiang, People's Republic of China.
authors.forename: Zhixun
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Colorectal Cancer Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People's Republic of China Colorectal Cancer Institute of Harbin Medical University, Harbin, Heilongjiang, People's Republic of China.
authors.forename: Shan
authors.initials: S
authors.lastname: Muhammad
authors.affiliation: Department of Colorectal Cancer Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People's Republic of China Colorectal Cancer Institute of Harbin Medical University, Harbin, Heilongjiang, People's Republic of China.
authors.forename: Guiyu
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Colorectal Cancer Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People's Republic of China Colorectal Cancer Institute of Harbin Medical University, Harbin, Heilongjiang, People's Republic of China.
authors.forename: Ying-gang
authors.initials: YG
authors.lastname: Chen
authors.affiliation: Department of Colorectal Cancer Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People's Republic of China Colorectal Cancer Institute of Harbin Medical University, Harbin, Heilongjiang, People's Republic of China wxshan1208@126.com.
authors.forename: Xishan
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D016147:Genes, Tumor Suppressor; D045325:HCT116 Cells; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics
chemical_list: C526297:IRS2 protein, human; D055504:Insulin Receptor Substrate Proteins; D035683:MicroRNAs; D051057:Proto-Oncogene Proteins c-akt