title: miR-93 functions as an oncomiR for the downregulation of PDCD4 in gastric carcinoma.
abstract: Programmed cell death 4 (PDCD4), as a tumor suppressor gene, is frequently reduced in a variety of tumors, including gastric cancer. Previous findings have indicated that PDCD4 participates in tumorigenesis through the regulation of apoptosis, but the molecular basis of this process has not been fully elucidated, and no studies have shown the upstream regulation of this gene in gastric cancer. In this study, we used bioinformatics analysis to search for miRNAs that could potentially target PDCD4 and identified miR-93 as a candidate. Moreover, we observed the inverse correlation between miR-93 and PDCD4 protein levels, but not mRNA levels, in human gastric cancer tissues. We further experimentally validated PDCD4 as the direct target of miR-93 by evaluating PDCD4 expression in gastric cancer cells after the overexpression or knockdown of miR-93. Additionally, the biological consequences of targeting PDCD4 through miR-93 were examined using cell apoptosis assays in vitro. We demonstrated that the repression of PDCD4 through miR-93 suppressed the apoptosis of gastric cancer cells. Finally, we revealed that miR-93 promoted the development of gastric tumor growth in xenograft mice by negatively regulating PDCD4. Taken together, the findings of the present study indicated the oncogenic role of miR-93 in gastric cancer tumorigenesis through targeting PDCD4, particularly in apoptosis.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, NJU Advanced Institute for Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life Science, Nanjing University, Nanjing, Jiangsu 210093, China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Liang
authors.affiliation: Department of General Surgery, The Affiliated Drum Tower Hospital of Medical School of Nanjing University and Nanjing Multi-center Biobank, Nanjing, Jiangsu 210008, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, NJU Advanced Institute for Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life Science, Nanjing University, Nanjing, Jiangsu 210093, China.
authors.forename: Danping
authors.initials: D
authors.lastname: Chu
authors.affiliation: Department of General Surgery, The Affiliated Drum Tower Hospital of Medical School of Nanjing University and Nanjing Multi-center Biobank, Nanjing, Jiangsu 210008, China.
authors.forename: Weijie
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Cardio-Thoracic Surgery, The Affiliated Drum Tower Hospital of Medical School of Nanjing University and Nanjing Multi-center Biobank, Nanjing, Jiangsu 210008, China.
authors.forename: Zhicong
authors.initials: Z
authors.lastname: Liao
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, NJU Advanced Institute for Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life Science, Nanjing University, Nanjing, Jiangsu 210093, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Fu
authors.affiliation: Department of Respiratory Medicine, The Affiliated Drum Tower Hospital of Medical School of Nanjing University and Nanjing Multi-center Biobank, Nanjing, Jiangsu 210008, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Yan
authors.affiliation: Department of Gastroenterology, The Affiliated Drum Tower Hospital of Medical School of Nanjing University and Nanjing Multi-center Biobank, Nanjing, Jiangsu 210008, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Endocrinology, Nanjing Municipal Hospital for Governmental Organizations, Nanjing, Jiangsu 210018, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, NJU Advanced Institute for Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life Science, Nanjing University, Nanjing, Jiangsu 210093, China.
authors.forename: Yujing
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, The Affiliated Drum Tower Hospital of Medical School of Nanjing University and Nanjing Multi-center Biobank, Nanjing, Jiangsu 210008, China.
authors.forename: Wenxian
authors.initials: W
authors.lastname: Guan
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, NJU Advanced Institute for Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life Science, Nanjing University, Nanjing, Jiangsu 210093, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D045744:Cell Line, Tumor; D015536:Down-Regulation; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D016513:Mice, SCID; D035683:MicroRNAs / Q000235:genetics*; D009857:Oncogenes / Q000235:genetics; D034622:RNA Interference; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014183:Transplantation, Heterologous; D047368:Tumor Burden / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D051017:Apoptosis Regulatory Proteins; C543350:MIRN93 microRNA, human; D035683:MicroRNAs; C114487:PDCD4 protein, human; D016601:RNA-Binding Proteins