PMID- 36852700 OWN - NLM STAT- MEDLINE DCOM- 20230307 LR - 20230319 IS - 1555-3892 (Electronic) IS - 0963-6897 (Print) IS - 0963-6897 (Linking) VI - 32 DP - 2023 Jan-Dec TI - Hypermethylation-Mediated lncRNA MAGI2-AS3 Downregulation Facilitates Malignant Progression of Laryngeal Squamous Cell Carcinoma via Interacting With SPT6. PG - 9636897231154574 LID - 10.1177/09636897231154574 [doi] LID - 09636897231154574 AB - Long noncoding RNAs (lncRNAs) have an effect on the occurrence and progression of a considerable number of diseases, especially cancer. Existing research has suggested that MAGI2 antisense RNA 3 (MAGI2-AS3) takes on a critical significance in the development of hepatocellular carcinoma and lung cancer. However, the functions of MAGI2-AS3 in laryngeal squamous cell carcinoma (LSCC) remain unclear. In this study, MAGI2-AS3 expression level in LSCC tissue and cell lines was detected, and the effect of MAGI2-AS3 overexpressed on LSCC phenotypes and the possible influence mechanisms were examined. MAGI2-AS3 was downregulated in the tissues of LSCC patients versus non-tumor tissues, and it was correlated with advanced TNM (tumor, node, metastasis) stage and lymph node metastases, as indicated by the results of this study. MAGI2-AS3 inhibited the proliferation, migration, and invasion of LSCC cells in vitro and in vivo. Furthermore, the hypermethylation level of the MAGI2-AS3 promoter region was indicated by bisulfite genomic sequencing and methylation-specific polymerase chain reaction, such that MAGI2-AS3 expression was downregulated. Besides, MAGI2-AS3 promoter hypermethylation was regulated by DNA methyltransferase 1 (DNMT1), and MAGI2-AS3 expression was reversed by 5-Aza-2'-deoxycytidine (5-Aza). Moreover, the result of the RNA pull-down experiment suggested that 38 proteins were enriched in the MAGI2-AS3 group versus the control group in TU177 cells. To be specific, SPT6 (ie, a conserved protein) was enriched by fold change >10. SPT6 knockdown reduced the antitumor effect of MAGI2-AS3 in TU177 and AMC-HN-8 cells. Meanwhile, SPT6 overexpression inhibited the proliferation, metastasis, and invasion of TU177 and AMC-HN-8 cells. As revealed by the above findings, DNMT1-regulated MAGI2-AS3 promoter hypermethylation led to downregulated MAGI2-AS3 expression, such that the presence and progression of LSCC were inhibited in an SPT6 binding-dependent manner. FAU - Wang, Jiantao AU - Wang J AD - Department of Otorhinolaryngology, The Second Hospital of Hebei Medical University, Shijiazhuang, China. FAU - Yang, Chuan AU - Yang C AD - Department of Otorhinolaryngology, The Second Hospital of Hebei Medical University, Shijiazhuang, China. FAU - Cao, Huan AU - Cao H AD - Department of Otorhinolaryngology, The Second Hospital of Hebei Medical University, Shijiazhuang, China. FAU - Yang, Jianwang AU - Yang J AD - Department of Otorhinolaryngology, The Second Hospital of Hebei Medical University, Shijiazhuang, China. FAU - Meng, Wenxia AU - Meng W AD - Department of Otorhinolaryngology, The Second Hospital of Hebei Medical University, Shijiazhuang, China. FAU - Yu, Miaomiao AU - Yu M AD - Department of Otorhinolaryngology, The Second Hospital of Hebei Medical University, Shijiazhuang, China. FAU - Yu, Lei AU - Yu L AD - Department of Otorhinolaryngology, The Second Hospital of Hebei Medical University, Shijiazhuang, China. FAU - Wang, Baoshan AU - Wang B AUID- ORCID: 0000-0002-2455-8338 AD - Department of Otorhinolaryngology, The Second Hospital of Hebei Medical University, Shijiazhuang, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Cell Transplant JT - Cell transplantation JID - 9208854 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 776B62CQ27 (Decitabine) RN - EC 2.7.4.8 (Guanylate Kinases) RN - EC 2.7.4.8 (MAGI2 protein, human) RN - 0 (RNA, Long Noncoding) RN - 0 (SUPT6H protein, human) SB - IM MH - Humans MH - Adaptor Proteins, Signal Transducing/genetics MH - Decitabine MH - Down-Regulation/genetics MH - Guanylate Kinases MH - *Head and Neck Neoplasms MH - *Liver Neoplasms MH - *RNA, Long Noncoding/genetics MH - Squamous Cell Carcinoma of Head and Neck PMC - PMC9986895 OTO - NOTNLM OT - DNA methylation OT - MAGI2-AS3 OT - SPT6 OT - biomarker OT - laryngeal squamous cell carcinoma COIS- The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. EDAT- 2023/03/01 06:00 MHDA- 2023/03/03 06:00 PMCR- 2023/02/28 CRDT- 2023/02/28 05:14 PHST- 2023/02/28 05:14 [entrez] PHST- 2023/03/01 06:00 [pubmed] PHST- 2023/03/03 06:00 [medline] PHST- 2023/02/28 00:00 [pmc-release] AID - 10.1177_09636897231154574 [pii] AID - 10.1177/09636897231154574 [doi] PST - ppublish SO - Cell Transplant. 2023 Jan-Dec;32:9636897231154574. doi: 10.1177/09636897231154574.