PMID- 37480618 OWN - NLM STAT- Publisher LR - 20230812 IS - 1879-1506 (Electronic) IS - 0003-9969 (Linking) VI - 154 DP - 2023 Oct TI - Long non-coding RNA SLC7A11 antisense RNA1 promotes oral squamous cell carcinoma progression by regulating ubiquitination of K-homology type splicing regulatory protein. PG - 105762 LID - S0003-9969(23)00150-4 [pii] LID - 10.1016/j.archoralbio.2023.105762 [doi] AB - OBJECTIVES: This article aims to elucidate the role of Long non-coding RNA SLC7A11 antisense RNA1 (SLC7A11-AS1) in oral squamous cell carcinoma, which are expected to be useful for the oral squamous cell carcinoma diagnosis and treatment. DESIGN: SLC7A11-AS1 expression was detected by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) in oral squamous cell carcinoma cell lines. Cellular localization of SLC7A11-AS1C was detected by fluorescence in situ hybridization (FISH) assays and subcellular fractionation assay. Biological functions of SLC7A11-AS1 were explored by 3-(4,5-dimethyl-2-thiazolyl)- 2,5-diphenyl-2-H-tetrazolium bromide (MTT), 5-ethynyl-2'-deoxyuridine (EdU), wounding healing, and transwell invasion assays in vitro, as well as mice xenograft experiments and metastasis assays in vivo. RNA pull-down, RNA immunoprecipitation, co-immunoprecipitation, ubiquitination assays, and rescue experiments were performed to determine the molecular mechanism of SLC7A11-AS1 in oral squamous cell carcinoma. RESULTS: SLC7A11-AS1 is overexpressed in oral cancer tissues and cell lines. Functionally, knockdown of SLC7A11-AS1 reduced the proliferation, migration, and invasion of oral squamous cell carcinoma cells in vitro and inhibited tumor growth as well as metastasis in vivo. Mechanistically, SLC7A11-AS1 impeded the interaction between K-homology type splicing regulatory protein (KHSRP) and kelch-like 12 (KLHL12), maintaining the stability of KHSRP by restraining KHSRP degradation through the ubiquitination-proteasome pathway. Furthermore, KHSRP overexpression recovered the malignant behaviors inhibited by SLC7A11-AS1 knockdown in oral cancer cells. CONCLUSION: SLC7A11-AS1 promoted oral squamous cell carcinoma development by interacting with KHSRP and maintaining KHSRP stability by preventing its degradation via the ubiquitination-proteasome pathway. Thus, SLC7A11-AS1 is a potential therapeutic target for oral cancer. CI - Copyright (c) 2023 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Liu, Zhen AU - Liu Z AD - Department of Stomatology, the Eighth Medical Center of Chinese PLA General Hospital, No.17 heishanhu Road, Haidian District, Beijing 100091, China. FAU - Wang, Xiaoyu AU - Wang X AD - Department of Stomatology, PLA Strategic Support Force Medical Center, No.9 Anxiang Beili, Deshengmenwai, Chaoyang District, Beijing 100101, China. FAU - Liu, Lin AU - Liu L AD - Department of Stomatology, the First Medical Center of Chinese PLA General Hospital, No.28 Fuxing Road, Haidian District, Beijing 100853, China. FAU - Guan, Miaosheng AU - Guan M AD - Department of Stomatology, PLA Rocket Force Characteristic Medical Center, No.16 Xinjiekou outside Street, Haidian District, Beijing 100088, China. FAU - Jiang, Hao AU - Jiang H AD - Department of Stomatology, the Eighth Medical Center of Chinese PLA General Hospital, No.17 heishanhu Road, Haidian District, Beijing 100091, China. FAU - An, Dan AU - An D AD - Department of Stomatology, the Eighth Medical Center of Chinese PLA General Hospital, No.17 heishanhu Road, Haidian District, Beijing 100091, China. FAU - Li, Hongbo AU - Li H AD - Department of Stomatology, the First Medical Center of Chinese PLA General Hospital, No.28 Fuxing Road, Haidian District, Beijing 100853, China. Electronic address: hongbo_l@sina.com. LA - eng PT - Journal Article DEP - 20230711 PL - England TA - Arch Oral Biol JT - Archives of oral biology JID - 0116711 SB - IM OTO - NOTNLM OT - Invasion OT - KH-type splicing regulatory protein OT - Migration OT - Oral squamous cell carcinoma OT - Proliferation OT - SLC7A11 antisense RNA1 COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/07/23 01:11 MHDA- 2023/07/23 01:11 CRDT- 2023/07/22 18:01 PHST- 2023/04/12 00:00 [received] PHST- 2023/06/21 00:00 [revised] PHST- 2023/07/03 00:00 [accepted] PHST- 2023/07/23 01:11 [pubmed] PHST- 2023/07/23 01:11 [medline] PHST- 2023/07/22 18:01 [entrez] AID - S0003-9969(23)00150-4 [pii] AID - 10.1016/j.archoralbio.2023.105762 [doi] PST - ppublish SO - Arch Oral Biol. 2023 Oct;154:105762. doi: 10.1016/j.archoralbio.2023.105762. Epub 2023 Jul 11.