PMID- 34408262 OWN - NLM STAT- MEDLINE DCOM- 20220321 LR - 20240226 IS - 2092-6413 (Electronic) IS - 1226-3613 (Print) IS - 1226-3613 (Linking) VI - 53 IP - 8 DP - 2021 Aug TI - LINC00319 promotes cancer stem cell-like properties in laryngeal squamous cell carcinoma via E2F1-mediated upregulation of HMGB3. PG - 1218-1228 LID - 10.1038/s12276-021-00647-2 [doi] AB - Laryngeal squamous cell carcinoma (LSCC) is one of the most common subtypes of head and neck malignancies worldwide. Long intervening/intergenic noncoding RNAs (LINCRNAs) have been recently implicated in various biological processes that take place in the setting of laryngeal cancer, but the regulatory role of LINC00319 in LSCC remains largely unknown. The current study aimed to elucidate the regulatory effect of LINC00319 on the development and progression of LSCC via high-mobility group box 3 (HMGB3). Microarray-based analysis was initially conducted to identify differentially expressed long noncoding RNAs, after which the expression of LINC00319 and HMGB3 in LSCC tissues and cells was determined accordingly. CD133(+)CD144(+) TU177 cells were subsequently isolated and transfected with LINC00319 overexpression vector (oe-LINC00319), short hairpin RNA (sh)-LINC00319, sh-HMGB3, sh-E2F transcription factor 1 (E2F1), and oe-E2F1, as well as their corresponding controls. The proliferative, invasion, self-renewal, and tumorigenic abilities of CD133(+)CD144(+) TU177 cells were then evaluated. Our in vitro findings were further confirmed following subcutaneous injection of cells expressing the corresponding plasmids into nude mice. LINC00319 and HMGB3 expressions were elevated in LSCC cells and tissues. LINC00319 increased HMGB3 expression by recruiting E2F1. Furthermore, the stimulatory role of LINC00319 on the proliferation, invasion, self-renewal ability, and tumorigenicity of CD133(+)CD144(+) TU177 cells was achieved by upregulating HMGB3 via recruitment of E2F1. The in vitro findings were also confirmed by in vivo experiments. Taken together, these data show that downregulating LINC00319 in CD133(+)CD144(+) TU177 cells may serve as a potential anticancer regimen by inhibiting the proliferation and invasion of cancer stem cells in LSCC. CI - (c) 2021. The Author(s). FAU - Yuan, Linlin AU - Yuan L AD - Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, People's Republic of China. FAU - Tian, Xiufen AU - Tian X AD - Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, People's Republic of China. FAU - Zhang, Yanfei AU - Zhang Y AD - Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, People's Republic of China. FAU - Huang, Xinhui AU - Huang X AD - Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, People's Republic of China. FAU - Li, Qing AU - Li Q AD - Department of Pathology, The Third Affiliated Hospital of Soochow University (Changzhou City No. 1 People's Hospital), 215006, Changzhou, People's Republic of China. FAU - Li, Wencai AU - Li W AD - Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, People's Republic of China. drli_liwencai@163.com. FAU - Li, Shenglei AU - Li S AD - Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, People's Republic of China. lishenglei@zzu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210818 PL - United States TA - Exp Mol Med JT - Experimental & molecular medicine JID - 9607880 RN - 0 (E2F1 Transcription Factor) RN - 0 (E2F1 protein, human) RN - 0 (HMGB3 Protein) RN - 0 (RNA, Long Noncoding) SB - IM MH - Animals MH - Carcinoma, Squamous Cell/*genetics MH - Cell Line, Tumor MH - Cell Proliferation/genetics MH - E2F1 Transcription Factor/*genetics/metabolism MH - *Gene Expression Regulation, Neoplastic MH - HMGB3 Protein/*genetics/metabolism MH - Humans MH - Laryngeal Neoplasms/*genetics/pathology MH - Mice, Inbred BALB C MH - Mice, Nude MH - Models, Biological MH - Neoplastic Stem Cells/metabolism/*pathology MH - Prognosis MH - RNA, Long Noncoding/genetics/*metabolism MH - Up-Regulation/*genetics MH - Mice PMC - PMC8417254 COIS- The authors declare no competing interests. EDAT- 2021/08/20 06:00 MHDA- 2022/03/22 06:00 PMCR- 2021/08/18 CRDT- 2021/08/19 06:29 PHST- 2019/04/20 00:00 [received] PHST- 2021/05/27 00:00 [accepted] PHST- 2021/04/09 00:00 [revised] PHST- 2021/08/20 06:00 [pubmed] PHST- 2022/03/22 06:00 [medline] PHST- 2021/08/19 06:29 [entrez] PHST- 2021/08/18 00:00 [pmc-release] AID - 10.1038/s12276-021-00647-2 [pii] AID - 647 [pii] AID - 10.1038/s12276-021-00647-2 [doi] PST - ppublish SO - Exp Mol Med. 2021 Aug;53(8):1218-1228. doi: 10.1038/s12276-021-00647-2. Epub 2021 Aug 18.