PMID- 36879410 OWN - NLM STAT- MEDLINE DCOM- 20230529 LR - 20230529 IS - 1460-2180 (Electronic) IS - 0143-3334 (Linking) VI - 44 IP - 2 DP - 2023 May 26 TI - Enhancer RNA IRS2e is essential for IRS2 expression and the oncogenic properties in oral squamous cell carcinoma. PG - 119-128 LID - 10.1093/carcin/bgad010 [doi] AB - The crucial roles of enhancer RNAs (eRNAs) in the regulation of gene expression in human diseases have drawn wider and wider attention in recent years. However, the specific expression profile and function of eRNAs are still rarely discussed in oral squamous cell carcinoma (OSCC), the most common subtype of head and neck squamous cell carcinoma (HNSC). In this study, we aimed to investigate the expression and function of an uncharacterized eRNA, insulin receptor substrate 2 enhancer RNA (IRS2e), in OSCC. We found that IRS2e was overexpressed in HNSC and its overexpression was positively correlated with a poor prognosis. The downregulation of IRS2e by short hairpin RNA significantly inhibited cell growth and induced cellular apoptosis and cell-cycle arrest in OSCC cells. Furthermore, the ablation of IRS2e inhibited tumor growth in vivo. Mechanically, IRS2e is essential for the expression of insulin receptor substrate 2 (IRS2), an oncogene nearby IRS2e in chromosome 13. Altogether, our study demonstrated that IRS2e is a novel oncogenic eRNA required for oncogene IRS2 expression in OSCC. CI - (c) The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com. FAU - Yan, Lingyan AU - Yan L AD - The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, 430079, China. FAU - Wang, Jiayun AU - Wang J AD - The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, 430079, China. FAU - Guo, Jihua AU - Guo J AUID- ORCID: 0000-0002-6713-4439 AD - The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, 430079, China. AD - Department of Endodontics, School and Hospital of Stomatology, Wuhan University, Wuhan, 430079, China. FAU - Jia, Rong AU - Jia R AUID- ORCID: 0000-0001-6960-6199 AD - The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, 430079, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Carcinogenesis JT - Carcinogenesis JID - 8008055 RN - 0 (Insulin Receptor Substrate Proteins) RN - 0 (RNA, Small Interfering) RN - 0 (IRS2 protein, human) SB - IM MH - Humans MH - Squamous Cell Carcinoma of Head and Neck/genetics MH - *Carcinoma, Squamous Cell/pathology MH - *Mouth Neoplasms/pathology MH - Insulin Receptor Substrate Proteins/genetics/metabolism MH - Cell Line, Tumor MH - Cell Proliferation/genetics MH - RNA, Small Interfering MH - *Head and Neck Neoplasms/genetics MH - Gene Expression Regulation, Neoplastic EDAT- 2023/03/08 06:00 MHDA- 2023/05/29 06:42 CRDT- 2023/03/07 00:13 PHST- 2022/11/15 00:00 [received] PHST- 2023/02/18 00:00 [revised] PHST- 2023/03/01 00:00 [accepted] PHST- 2023/05/29 06:42 [medline] PHST- 2023/03/08 06:00 [pubmed] PHST- 2023/03/07 00:13 [entrez] AID - 7069775 [pii] AID - 10.1093/carcin/bgad010 [doi] PST - ppublish SO - Carcinogenesis. 2023 May 26;44(2):119-128. doi: 10.1093/carcin/bgad010.