Published on Aug. 28, 2018 in Cancer Lett volume 430DP - 2018 Aug 28TI - Novel long noncoding RNA NMR promotes tumor progression via NSUN2 and BPTF inesophageal squamous cell carcinoma.PG - 57-66LID - S0304-3835(18)30338-0 [pii]LID - 10.1016/j.canlet.2018.05.013 [doi]AB - Long noncoding RNAs (lncRNA) have been implicated in cancer but most of them remainlargely unstudied. Here, we identified a novel NSUN2 methylated lncRNA (NMR), whichwas significantly upregulated in esophageal squamous cell carcinoma (ESCC),functioned as a key regulator of ESCC tumor metastasis and drug resistance.Upregulation of NMR correlated with tumor metastasis and indicated poor overallsurvival in ESCC patients. Functionally, NMR could promote tumor cell migration andinvasion, inhibit cisplatin-induced apoptosis and increase drug resistance in ESCCcells. Mechanistically, transcription of NMR could be upregulated by NF-κBactivation after IL-1β and TNF-α treatment. NMR was methylated by NSUN2 and mightcompetitively inhibit methylation of potential mRNAs. NMR could directly bind tochromatin regulator BPTF, and potentially promote MMP3 and MMP10 expression byERK1/2 pathway through recruiting BPTF to chromatin. Taken together, NMR functionsas an oncogenic gene and may serve as new biomarker and therapeutic target in ESCC.CI - Copyright © 2018 Elsevier B.V. All rights reserved.FAU - Li, YuanAU - Li YAD - Department of Thoracic Surgery, National Cancer Center/Cancer Hospital, ChineseAcademy of Medical Sciences and Peking Union Medical College, Beijing, 100021,China.FAU - Li, JiagenAU - Li JAD - Department of Thoracic Surgery, National Cancer Center/Cancer Hospital, ChineseAcademy of Medical Sciences and Peking Union Medical College, Beijing, 100021,China.FAU - Luo, MeiAU - Luo MAD - Central Laboratory, Beijing Luhe Hospital, Capital Medical University, Beijing,China.FAU - Zhou, ChengchengAU - Zhou CAD - Department of Thoracic Surgery, National Cancer Center/Cancer Hospital, ChineseAcademy of Medical Sciences and Peking Union Medical College, Beijing, 100021,China.FAU - Shi, XuejiaoAU - Shi XAD - Department of Thoracic Surgery, National Cancer Center/Cancer Hospital, ChineseAcademy of Medical Sciences and Peking Union Medical College, Beijing, 100021,China.FAU - Yang, WenhuiAU - Yang WAD - Department of Biochemistry and Molecular Biology, Shanxi Medical University,Taiyuan, Shanxi, 030001, China; Tumor Hospital of Shanxi Province, Taiyuan, Shanxi,030013, China.FAU - Lu, ZhiliangAU - Lu ZAD - Department of Thoracic Surgery, National Cancer Center/Cancer Hospital, ChineseAcademy of Medical Sciences and Peking Union Medical College, Beijing, 100021,China.FAU - Chen, ZhaoliAU - Chen ZAD - Department of Thoracic Surgery, National Cancer Center/Cancer Hospital, ChineseAcademy of Medical Sciences and Peking Union Medical College, Beijing, 100021,China.FAU - Sun, NanAU - Sun NAD - Department of Thoracic Surgery, National Cancer Center/Cancer Hospital, ChineseAcademy of Medical Sciences and Peking Union Medical College, Beijing, 100021,China. Electronic address: sunnan@vip.126.com.FAU - He, JieAU - He JAD - Department of Thoracic Surgery, National Cancer Center/Cancer Hospital, ChineseAcademy of Medical Sciences and Peking Union Medical College, Beijing, 100021,China. Electronic address: prof.jiehe@gmail.com.LA - engPT - Journal ArticlePT - Research Support, Non-U.S. Gov'tDEP - 20180512PL - IrelandTA - Cancer LettJT - Cancer lettersJID - 7600053RN - 0 (Antigens, Nuclear)RN - 0 (Biomarkers, Tumor)RN - 0 (Chromatin)RN - 0 (Nerve Tissue Proteins)RN - 0 (RNA, Long Noncoding)RN - 0 (RNA, Messenger)RN - 0 (Transcription Factors)RN - 0 (fetal Alzheimer antigen)RN - EC 2.1.1.- (Methyltransferases)RN - EC 2.1.1.- (NSUN2 protein, human)MH - AdultMH - AgedMH - Antigens, Nuclear/*genetics/metabolismMH - Biomarkers, Tumor/*metabolismMH - Chromatin/metabolismMH - Disease ProgressionMH - Esophageal Neoplasms/*genetics/mortality/pathologyMH - Esophageal Squamous Cell Carcinoma/*genetics/mortality/pathologyMH - Esophagus/pathologyMH - FemaleMH - Gene Expression Regulation, NeoplasticMH - HumansMH - Kaplan-Meier EstimateMH - MaleMH - MethylationMH - Methyltransferases/*metabolismMH - Middle AgedMH - Nerve Tissue Proteins/*genetics/metabolismMH - OncogenesMH - RNA, Long Noncoding/*metabolismMH - RNA, Messenger/metabolismMH - Sequence Analysis, RNAMH - Tissue Array AnalysisMH - Transcription Factors/*genetics/metabolismMH - Up-RegulationOTO - NOTNLMOT - *Drug resistanceOT - *ESCCOT - *LncRNAsOT - *MetastasisOT - *OncogenesisEDAT- 2018/05/16 06:00MHDA- 2019/08/06 06:00CRDT- 2018/05/16 06:00PHST- 2018/03/04 00:00 [received]PHST- 2018/05/05 00:00 [revised]PHST- 2018/05/10 00:00 [accepted]PHST- 2018/05/16 06:00 [pubmed]PHST- 2019/08/06 06:00 [medline]PHST- 2018/05/16 06:00 [entrez]AID - S0304-3835(18)30338-0 [pii]AID - 10.1016/j.canlet.2018.05.013 [doi]PST - ppublishSO - Cancer Lett. 2018 Aug 28;430:57-66. doi: 10.1016/j.canlet.2018.05.013. Epub 2018 May12.</pre></div></body></html>().
PubMed ID: 29763634
DOI: S0304-3835(18)30338-0
Abstract:
Long noncoding RNAs (lncRNA) have been implicated in cancer but most of them remainlargely unstudied. Here, we identified a novel NSUN2 methylated lncRNA (NMR), whichwas significantly upregulated in esophageal squamous cell carcinoma (ESCC),functioned as a key regulator of ESCC tumor metastasis and drug resistance.Upregulation of NMR correlated with tumor metastasis and indicated poor overallsurvival in ESCC patients. Functionally, NMR could promote tumor cell migration andinvasion, inhibit cisplatin-induced apoptosis and increase drug resistance in ESCCcells. Mechanistically, transcription of NMR could be upregulated by NF-κBactivation after IL-1β and TNF-α treatment. NMR was methylated by NSUN2 and mightcompetitively inhibit methylation of potential mRNAs. NMR could directly bind tochromatin regulator BPTF, and potentially promote MMP3 and MMP10 expression byERK1/2 pathway through recruiting BPTF to chromatin. Taken together, NMR functionsas an oncogenic gene and may serve as new biomarker and therapeutic target in ESCC.CI - Copyright © 2018 Elsevier B.V. All rights reserved.