PMID- 33551645 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220420 IS - 1179-1322 (Print) IS - 1179-1322 (Electronic) IS - 1179-1322 (Linking) VI - 13 DP - 2021 TI - LncRNA GAS5 Suppressed Proliferation and Promoted Apoptosis in Laryngeal Squamous Cell Carcinoma by Targeting MiR-26a-5p and Modifying ULK2. PG - 871-887 LID - 10.2147/CMAR.S250778 [doi] AB - PURPOSE: Long noncoding RNAs growth arrest-specific 5 (GAS5) exerts important functions in modulating various tumor behaviors. However, the role of lncRNA GAS5 in laryngeal squamous cell carcinoma (LSCC) remains unknown. MATERIALS AND METHODS: Cell viability and apoptosis were, respectively, detected by cell counting kit-8 and flow cytometry, DIANA-LncBase V, Starbase, TargetScan and a dual-luciferase reporter gene assay were employed to assess the relationship among GAS5, miR-26a-5p and uncoordinated 51-like kinase 1 (ULK2), and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot were performed to detect the expression of autophagy-relative factors. RESULTS: The expression level of GAS5 was frequently decreased in LSCC cell lines, and up-regulated GAS5 inhibited AMC-HN-8 cells viability and induced apoptosis. More importantly, we found that GAS5 activated autophagy, with enhanced autophagy-related proteins after GAS5 overexpression. While down-regulated GAS5 had opposite results in Tu 177 cells, GAS5 was found to act as a microRNA sponge in a pathway to regulate miR-26a-5p and its target gene ULK2. MiR-26a-5p mimics inhibited apoptosis and autophagy, which were reversed by GAS5 and siGAS5 in AMC-HN-8 cells and Tu 177 cells, as well as ULK2 in AMC-HN-8 cells. Meanwhile, the concomitant downregulation of ULK2 and miRNA-26a-5p inhibitor decreased the miRNA-26a-5p inhibitor-induced apoptosis and autophagy. CONCLUSION: This is the first report of LncRNA GAS5 acting as a tumor suppressor in LSCC by regulating the miR-26a-5p/ULK2 axis, and it could be a new target for gene therapy in LSCC. CI - (c) 2021 Wang et al. FAU - Wang, Jian AU - Wang J AD - Department of Head and Neck Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, People's Republic of China. FAU - Zhu, Yiming AU - Zhu Y AD - Department of Head and Neck Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, People's Republic of China. FAU - Ni, Song AU - Ni S AD - Department of Head and Neck Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, People's Republic of China. FAU - Liu, Shaoyan AU - Liu S AD - Department of Head and Neck Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, People's Republic of China. LA - eng PT - Journal Article DEP - 20210129 PL - New Zealand TA - Cancer Manag Res JT - Cancer management and research JID - 101512700 PMC - PMC7856352 OTO - NOTNLM OT - apoptosis OT - autophagy OT - laryngeal squamous cell carcinoma OT - long noncoding RNAs growth arrest-specific 5 OT - miR-26a-5p COIS- The authors declare no conflicts of interest. EDAT- 2021/02/09 06:00 MHDA- 2021/02/09 06:01 PMCR- 2021/01/29 CRDT- 2021/02/08 05:34 PHST- 2020/02/21 00:00 [received] PHST- 2020/07/18 00:00 [accepted] PHST- 2021/02/08 05:34 [entrez] PHST- 2021/02/09 06:00 [pubmed] PHST- 2021/02/09 06:01 [medline] PHST- 2021/01/29 00:00 [pmc-release] AID - 250778 [pii] AID - 10.2147/CMAR.S250778 [doi] PST - epublish SO - Cancer Manag Res. 2021 Jan 29;13:871-887. doi: 10.2147/CMAR.S250778. eCollection 2021.