The aspirin-induced long non-coding RNA OLA1P2 blocks phosphorylated STAT3 homodimer formation

Genome Biology
Haiyan GuoJianjun Zhang

Abstract

Although the chemopreventive effects of aspirin have been extensively investigated, the roles of many cell components, such as long non-coding RNAs, in these effects are still not completely understood. We identify an aspirin-induced upregulated lncRNA, OLA1P2, in human colorectal cancer. Aspirin induces demethylation of the FOXD3 promoter and promotes expression of the FOXD3 gene. Subsequently, upregulated FOXD3 protein transcriptionally activates lncRNA OLA1P2 expression. OLA1P2 upregulation markedly affects STAT3 signaling pathway activity by inhibiting the nuclear import of phosphorylated STAT3. The phosphorylation of tyrosine-705 of STAT3 is the first step in OLA1P2 binding, and the formation of phosphorylated STAT3 homodimers is subsequently blocked. OLA1P2 interacts directly with STAT3 due to OLA1P2 sharing the same conservative STAT3 transcription response element as STAT3 targets. Regular use of aspirin dramatically decreases the number of metastatic nodules of cancer cells in immunodeficient mouse lungs, and OLA1P2 silencing markedly weakens the anti-metastatic activity of aspirin in the lungs. Additionally, low OLA1P2 levels are associated with malignant transformation and lower overall survival in cancers. The prese...Continue Reading

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Citations

Jun 29, 2016·Cytokine·Jan PencikLukas Kenner
Jun 2, 2018·Medicinal Research Reviews·Hui HuaYangfu Jiang
Jul 27, 2017·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Jiwei ZhangXianghuo He
Mar 1, 2018·BMC Gastroenterology·Thorbjørn Søren Rønn JensenNiels Bindslev
Jan 18, 2019·Journal of Cellular Physiology·Ye WangBangruo Qi
Oct 15, 2019·Journal of Cellular Physiology·Changjie LouYanqiao Zhang
Feb 17, 2017·Biochemical Society Transactions·Aldema Sas-ChenYosef Yarden
Nov 14, 2019·International Journal of Molecular Sciences·Xiaopei ZhangFafu Shen
Sep 29, 2020·Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy·Songjia LaiShiyi Chen
Jul 6, 2019·Journal of Clinical Laboratory Analysis·Rongjia ZhouHaojun Chen
May 8, 2019·Applied Microbiology and Biotechnology·Chit TamTzi Bun Ng
Feb 2, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Rasmi R MishraÖzgür Şahin
Jun 24, 2018·Cancer Research·Hailong PeiTom K Hei
Feb 13, 2021·International Journal of Molecular Sciences·Marco BocchettiAlessia Maria Cossu
Dec 29, 2020·Cancer Biomarkers : Section a of Disease Markers·Huiping TanXiangbing Jiang
May 6, 2019·Biochemical and Biophysical Research Communications·Cuixia BianHuirong Gai
Apr 8, 2021·Acta Pharmacologica Sinica·Fei-Fei XuLi-Hong Ye
Aug 11, 2021·Cancer Cell International·Qian LuHongming Pan
Aug 28, 2021·International Journal of Obesity : Journal of the International Association for the Study of Obesity·Juan LiGuo Zhang
Aug 10, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Xiaoting LinFeng Ye
Jan 19, 2022·Clinical and Translational Medicine·Serena Wooten, Keriayn N Smith

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Datasets Mentioned

BETA
GSE76583

Methods Mentioned

BETA
pull-down
immunoprecipitation
PCR
RIP
electrophoresis
dissection
pull down
ChIP
transfection
immunoprecipitation assay

Software Mentioned

GeneSpring
Feature Extraction
GSEA

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