EGR1 interacts with DNMT3L to inhibit the transcription of miR-195 and plays an anti-apoptotic role in the development of gastric cancer

Journal of Cellular and Molecular Medicine
Yang YangChen Huang

Abstract

EGR1 regulates the expression of its downstream target genes and may exert different biological effects in different tumours. We found that the expression of EGR1 was increased in gastric cancer (GC), and silencing the expression of EGR1 promoted the apoptosis of GC cells. Moreover, overexpression of EGR1 repressed the apoptosis of GC cells. Bioinformatics analysis showed that EGR1 had binding sites at the upstream promoter region of miR-195; ChIP assays were applied to determine EGR1 occupancy of the miR-195 promoter. The RT-PCR results showed that EGR1 suppressed the expression of miR-195. The mechanism by which EGR1 acts as a transcriptional repressor is still unclear. Bioinformatics analysis showed that EGR1 may interact with DNMT3L. We confirmed that EGR1 and DNMT3L formed a complex, and EGR1 was an important player in the transcriptional control of miR-195. Overexpression of miR-195 inhibited proliferation and promoted apoptosis in GC cells. We found a well-matched miR-195 binding site at the AKT3 3'-UTR. Double luciferase reporter assays showed that AKT3 was a target of miR-195, and silencing AKT3 repressed cell proliferation and promoted apoptosis. Our results indicated EGR1 may interact with DNMT3L to inhibit the miR-1...Continue Reading

Citations

Aug 31, 2002·Nucleic Acids Research·Rachel DeplusFrançois Fuks
Mar 24, 2005·Journal of Cellular and Molecular Medicine·Gang SongShideng Bao
May 13, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Kahori MinamiKeisei Okamoto
Jan 10, 2013·Current Cancer Drug Targets·Mitchell Cheung, Joseph R Testa
Jan 24, 2014·International Journal of Molecular Sciences·Karin ZinsSeyedhossein Aharinejad
Mar 22, 2014·Biomedical Reports·Miao HeZi-Wei Wang
May 27, 2015·PloS One·Yi FengFrancisco J Naya
Jan 26, 2016·CA: a Cancer Journal for Clinicians·Wanqing ChenJie He
May 14, 2016·Oncology Reports·Xiaowen ZhangMing Chen
May 21, 2016·International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society·Quan ZhouYan Li
Jul 6, 2016·Breast Cancer Research and Treatment·Ming YangQipeng Yuan
Jan 31, 2017·Molecular Therapy : the Journal of the American Society of Gene Therapy·Ming SunKai-Hua Lu
May 19, 2017·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Lei YanKerui Cai
Oct 21, 2017·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Junyan YuRong Zhang
Jan 14, 2018·Molecular Cancer Research : MCR·Shuhei EnjojiKoichi Sato
Sep 7, 2018·Cancer Cell International·Yong-Xia WangYu-Han Hu
Jun 1, 2016·International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society·Quan ZhouYan Li

Related Concepts

Genes
Malignant Neoplasm of Stomach
Regulation of Biological Process
Transcription, Genetic
Neoplasms
Promoter
Bio-Informatics
Reverse Transcriptase Polymerase Chain Reaction
Chromatin Immunoprecipitation
Cell Proliferation

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis