PMID- 34003510 OWN - NLM STAT- MEDLINE DCOM- 20210819 LR - 20240226 IS - 1098-2744 (Electronic) IS - 0899-1987 (Linking) VI - 60 IP - 7 DP - 2021 Jul TI - The LncRNA FGD5-AS1/miR-497-5p axis regulates septin 2 (SEPT2) to accelerate cancer progression and increase cisplatin-resistance in laryngeal squamous cell carcinoma. PG - 469-480 LID - 10.1002/mc.23305 [doi] AB - Aberrant expression or mutation of the Septin gene family is closely associated with cancer progression, and septin 2 (SEPT2) exerts its tumor-promoting effects in multiple cancers, but its role in regulating laryngeal squamous cell carcinoma (LSCC) progression and drug resistance has not been investigated. Based on the published data, the present study identified that SEPT2 promoted cancer progression and increased cisplatin-resistance in LSCC, and a novel LncRNA FGD5-AS1/miR-497-5p axis was crucial for this process. Mechanistically, SEPT2 tended to be enriched in LSCC tissues and cells, and knock-down of SEPT2 inhibited cell proliferation, viability, migration, and tumorigenesis in LSCC cells in vitro and in vivo. Aside from that, SEPT2 overexpression increased cisplatin resistance in LSCC cells. Next, by conducting the dual-luciferase reporter gene system assay, we identified that the LncRNA FGD5-AS1/miR-497-5p axis regulated SEPT2 in LSCC. Specifically, LncRNA FGD5-AS1 sponged miR-497-5p to upregulate SEPT2 in LSCC cells in a competing endogenous RNA (ceRNA) mechanisms-dependent manner. Interestingly, upregulated LncRNA FGD5-AS1 and downregulated miR-497-5p were observed in LSCC tissues and cells, and LncRNA FGD5-AS1 ablation inhibited cancer progression. Also, LncRNA FGD5-AS1 overexpression increased cisplatin-resistance in LSCC by modulating the miR-497-5p/SEPT2 axis. Collectively, we conclude that targeting the LncRNA FGD5-AS1/miR-497-5p/SEPT2 signaling cascade may be an alternative strategy to treat LSCC in the clinic. CI - (c) 2021 Wiley Periodicals LLC. FAU - Song, Kaibin AU - Song K AD - Department of Head and Neck Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China. FAU - Yu, Pingyang AU - Yu P AD - Department of Head and Neck Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China. FAU - Zhang, Cong AU - Zhang C AD - Department of Head and Neck Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China. FAU - Yuan, Zhennan AU - Yuan Z AUID- ORCID: 0000-0001-5832-6562 AD - Department of Head and Neck Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China. FAU - Zhang, Hailin AU - Zhang H AD - Department of Head and Neck Surgery, Hunan Cancer Hospital, Changsha, Hunan, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210518 PL - United States TA - Mol Carcinog JT - Molecular carcinogenesis JID - 8811105 RN - 0 (3' Untranslated Regions) RN - 0 (MIRN497 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (RNA, Long Noncoding) RN - EC 3.6.1.- (SEPTIN2 protein, human) RN - EC 3.6.1.- (Septins) RN - Q20Q21Q62J (Cisplatin) SB - IM MH - 3' Untranslated Regions MH - Animals MH - Cell Line, Tumor MH - Cisplatin/pharmacology MH - Drug Resistance, Neoplasm/genetics MH - Female MH - Gene Expression Regulation, Neoplastic/drug effects MH - Head and Neck Neoplasms/drug therapy/genetics/*pathology MH - Humans MH - Mice, Inbred BALB C MH - MicroRNAs/*genetics MH - RNA, Long Noncoding/*genetics MH - Septins/*genetics/metabolism MH - Squamous Cell Carcinoma of Head and Neck/drug therapy/genetics/*pathology MH - Xenograft Model Antitumor Assays MH - Mice OTO - NOTNLM OT - LncRNA FGD5-AS1 OT - cancer biology OT - laryngeal carcinoma OT - miR-497-5p OT - septin 2 EDAT- 2021/05/19 06:00 MHDA- 2021/08/20 06:00 CRDT- 2021/05/18 12:27 PHST- 2021/04/14 00:00 [revised] PHST- 2020/12/18 00:00 [received] PHST- 2021/04/21 00:00 [accepted] PHST- 2021/05/19 06:00 [pubmed] PHST- 2021/08/20 06:00 [medline] PHST- 2021/05/18 12:27 [entrez] AID - 10.1002/mc.23305 [doi] PST - ppublish SO - Mol Carcinog. 2021 Jul;60(7):469-480. doi: 10.1002/mc.23305. Epub 2021 May 18.