title: MiR-101 inhibits cell growth and tumorigenesis of Helicobacter pylori related gastric cancer by repression of SOCS2.
abstract: Several microRNAs (miRNA) have been implicated in H. pylori related gastric cancer (GC). However, the molecular mechanism of miRNAs in gastric cancer has not been fully understood. In this study, we reported that miR-101 is significantly down-regulated in H. pylori positive tissues and cells and in tumor tissues with important functional consequences. Ectopic expression of miR-101 dramatically suppressed cell proliferation and colony formation by inducing G1-phase cell-cycle arrest. We found that miR-101 strongly reduced the expression of SOCS2 oncogene in GC cells. Similar to the restoring miR-26 expression, SOCS2 down-regulation inhibited cell growth and cell-cycle progression, whereas SOCS2 over-expression rescued the suppressive effect of miR-101. Mechanistic investigations revealed that miR-101 suppressed the expression of c-myc, CDK2, CDK4, CDK6, CCND2, CCND3, and CCNE2, while promoted tumor suppressor p14, p16, p21 and p27 expression. In clinical specimens, SOCS2 was over-expressed in tumors and H. pylori positive tissues and its mRNA levels were inversely correlated with miR-101 expression. Taken together, our results indicated that miR-101 functions as a growth-suppressive miRNA in H. pylori related GC, and that its suppressive effects are mediated mainly by repressing SOCS2 expression.
authors.affiliation: a Department of Gastroenterology ; First Affiliated Hospital of Nanjing Medical University ; Nanjing , China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Zhou
authors.forename: Yang
authors.initials: Y
authors.lastname: Xia
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.forename: Guoxin
authors.initials: G
authors.lastname: Zhang
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004195:Disease Models, Animal; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D016481:Helicobacter Infections / Q000150:complications*; D016480:Helicobacter pylori; D064593:Heterografts; D006801:Humans; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D034622:RNA Interference; D013274:Stomach Neoplasms / Q000209:etiology* / Q000473:pathology*; D050826:Suppressor of Cytokine Signaling Proteins / Q000737:chemistry / Q000235:genetics*; D047368:Tumor Burden
chemical_list: D020413:3' Untranslated Regions; C534072:MIRN101 microRNA, human; D035683:MicroRNAs; C106643:SOCS2 protein, human; D050826:Suppressor of Cytokine Signaling Proteins
keywords: CDK, cyclin-dependent kinase; GC, gastric cancer; Helicobacter pylori; MOI, multiplicity of infection; PVDF, polyvinylidene difluoride; UTR, untranslated regions; cell growth; cell-cycle regulators; gastric cancer; miR-101; SOCS2; miRNA, microRNA; mt, mutant; qRT-PCR, quantitative real-time; tumorigenesis; wt, wild-type