Published on March 20, 2020 in Gene volume 731DP - 2020 Mar 20TI - N(6)-methyladenosine ALKBH5 promotes non-small cell lung cancer progress byregulating TIMP3 stability.PG - 144348LID - S0378-1119(20)30017-2 [pii]LID - 10.1016/j.gene.2020.144348 [doi]AB - Mounting evidence demonstrates that N(6)-methyladenosine (m(6)A) play critical rolesof m(6)A in the epigenetic regulation, especially for human cancer. The m(6)Amodification is installed by methyltransferase and erased demethylases, leading tothe significant modification for gene expression and cell fate. Here, weinvestigated the biological roles and mechanism of demethylase alkylation repairhomolog protein 5 (ALKBH5) in the non-small cell lung cancer (NSCLC). Resultsrevealed that ALKBH5 was ectopically up-regulated in the NSCLC tissue and cells, andclosely correlated with the poor prognosis. Functionally, ALKBH5 promoted theproliferation and reduced apoptosis of NSCLC cells in vitro, and knockdown of ALKBH5repressed the tumor growth in vivo. Mechanistically, RNA immunoprecipitationsequencing (RIP-Seq) revealed that ALKBH5 targeted the TIMP3. Moreover, ALKBH5repressed TIMP3 mRNA stability and protein production. In conclusion, the presentresearch confirmed the ALKBH5/TIMP3 pathway in the NSCLC oncogenesis progress,providing a novel insight for the epitranscriptome and potential therapeutic targetfor NSCLC.CI - Copyright © 2020. Published by Elsevier B.V.FAU - Zhu, ZhiyuanAU - Zhu ZAD - Department of Oncology, First People&#39;s Hospital of Yancheng, Fourth AffiliatedHospital of Nantong University, Yancheng, Jiangsu, China.FAU - Qian, QiAU - Qian QAD - Department of Oncology, First People&#39;s Hospital of Yancheng, Fourth AffiliatedHospital of Nantong University, Yancheng, Jiangsu, China.FAU - Zhao, XiaAU - Zhao XAD - Department of Oncology, First People&#39;s Hospital of Yancheng, Fourth AffiliatedHospital of Nantong University, Yancheng, Jiangsu, China.FAU - Ma, LiangAU - Ma LAD - Department of Oncology, First People&#39;s Hospital of Yancheng, Fourth AffiliatedHospital of Nantong University, Yancheng, Jiangsu, China.FAU - Chen, PingAU - Chen PAD - Department of Oncology, First People&#39;s Hospital of Yancheng, Fourth AffiliatedHospital of Nantong University, Yancheng, Jiangsu, China. Electronic address:chenpingdoctor@yeah.net.LA - engPT - Journal ArticleDEP - 20200109PL - NetherlandsTA - GeneJT - GeneJID - 7706761RN - 0 (RNA, Messenger)RN - 0 (TIMP3 protein, human)RN - 0 (Tissue Inhibitor of Metalloproteinase-3)RN - 1867-73-8 (N6-methyladenosine (m6A))RN - EC 1.14.11.- (ALKBH5 protein, human)RN - EC 1.14.11.- (AlkB Homolog 5, RNA Demethylase)RN - K72T3FS567 (Adenosine)SB - IMMH - A549 CellsMH - Adenosine/*analogs &amp; derivatives/metabolismMH - AlkB Homolog 5, RNA Demethylase/genetics/*metabolism/*physiologyMH - AnimalsMH - Carcinogenesis/geneticsMH - Carcinoma, Non-Small-Cell Lung/*genetics/metabolism/pathologyMH - Cell Line, TumorMH - Disease ProgressionMH - Epigenesis, Genetic/physiologyMH - Gene Expression Regulation, NeoplasticMH - HumansMH - Lung Neoplasms/*genetics/metabolism/pathologyMH - MaleMH - MiceMH - Mice, Inbred BALB CMH - Mice, NudeMH - RNA Stability/*geneticsMH - RNA, Messenger/metabolismMH - Tissue Inhibitor of Metalloproteinase-3/*geneticsOTO - NOTNLMOT - ALKBH5OT - M(6)AOT - Non-small cell lung cancerOT - TIMP3COIS- Declaration of Competing Interest The authors declare that they have no knowncompeting financial interests or personal relationships that could have appeared toinfluence the work reported in this paper.EDAT- 2020/01/14 06:00MHDA- 2020/02/28 06:00CRDT- 2020/01/14 06:00PHST- 2019/09/07 00:00 [received]PHST- 2020/01/06 00:00 [revised]PHST- 2020/01/07 00:00 [accepted]PHST- 2020/01/14 06:00 [pubmed]PHST- 2020/02/28 06:00 [medline]PHST- 2020/01/14 06:00 [entrez]AID - S0378-1119(20)30017-2 [pii]AID - 10.1016/j.gene.2020.144348 [doi]PST - ppublishSO - Gene. 2020 Mar 20;731:144348. doi: 10.1016/j.gene.2020.144348. Epub 2020 Jan 9.</pre></div></body></html>().

PubMed ID: 31927006

DOI: S0378-1119(20)30017-2


Abstract:

Mounting evidence demonstrates that N(6)-methyladenosine (m(6)A) play critical rolesof m(6)A in the epigenetic regulation, especially for human cancer. The m(6)Amodification is installed by methyltransferase and erased demethylases, leading tothe significant modification for gene expression and cell fate. Here, weinvestigated the biological roles and mechanism of demethylase alkylation repairhomolog protein 5 (ALKBH5) in the non-small cell lung cancer (NSCLC). Resultsrevealed that ALKBH5 was ectopically up-regulated in the NSCLC tissue and cells, andclosely correlated with the poor prognosis. Functionally, ALKBH5 promoted theproliferation and reduced apoptosis of NSCLC cells in vitro, and knockdown of ALKBH5repressed the tumor growth in vivo. Mechanistically, RNA immunoprecipitationsequencing (RIP-Seq) revealed that ALKBH5 targeted the TIMP3. Moreover, ALKBH5repressed TIMP3 mRNA stability and protein production. In conclusion, the presentresearch confirmed the ALKBH5/TIMP3 pathway in the NSCLC oncogenesis progress,providing a novel insight for the epitranscriptome and potential therapeutic targetfor NSCLC.CI - Copyright © 2020. Published by Elsevier B.V.



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