PMID- 37816718 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20231123 IS - 2058-7716 (Print) IS - 2058-7716 (Electronic) IS - 2058-7716 (Linking) VI - 9 IP - 1 DP - 2023 Oct 10 TI - IGF2BP2 acts as a m(6)A modification regulator in laryngeal squamous cell carcinoma through facilitating CDK6 mRNA stabilization. PG - 371 LID - 10.1038/s41420-023-01669-7 [doi] LID - 371 AB - Laryngeal squamous cell carcinoma (LSCC) is one of the most commonly seen cancers in the head and neck region with increasing morbidity and mortality globally. N6-methyladenosine (m(6)A) modification plays a critical role in the carcinogenesis of LSCC. In this study, two datasets from online database were analyzed for differentially expressed genes (DEGs) between LSCC and normal samples. Furthermore, we carried out a series of experiments, including hematoxylin & eosin staining, immunohistochemical (IHC) staining, CCK-8, colony formation, transwell, flow cytometry, xenograft tumor model assays, actinomycin D assay, cycloheximide (CHX) assay, methylated m(6)A RNA immunoprecipitation (Me-RIP), RNA immunoprecipitation (RIP) assay, to verify the relevant findings in vivo and in vitro. Insulin like growth factor 2 mRNA binding protein 2 (IGF2BP2) was identified as an up-regulated m(6)A regulator in LSCC samples. Lower IGF2BP2 expression was linked to higher survival probability in LSCC and other head and neck squamous cell carcinoma patients. In LSCC cells, IGF2BP2 knockdown attenuated cancer cell aggressiveness, possibly through modulating cell cycle arrest. In the xenograft tumor model derived from IGF2BP2 knocked-down LSCC cells, IGF2BP2 knockdown inhibited tumor growth. IGF2BP2 up-regulated CDK6 expression through facilitating the stability of CDK6 mRNA and protein. CDK6 knockdown caused no changes in IGF2BP2 expression, but partially eliminated the promotive effects of IGF2BP2 overexpression on LSCC cells' aggressiveness. Overexpressed IGF2BP2 in LSCC serves as an oncogenic factor, promoting LSCC cell proliferation and invasion in vitro and tumor growth in a xenograft tumor model in vivo through facilitating CDK6 mRNA stabilization. CI - (c) 2023. Cell Death Differentiation Association (ADMC). FAU - Tang, Xiaojun AU - Tang X AD - Department of Otolaryngology Head and Neck Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China. FAU - Tang, Qinglai AU - Tang Q AD - Department of Otolaryngology Head and Neck Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China. FAU - Li, Shisheng AU - Li S AD - Department of Otolaryngology Head and Neck Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China. FAU - Li, Mengmeng AU - Li M AD - Department of Otolaryngology Head and Neck Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China. FAU - Yang, Tao AU - Yang T AUID- ORCID: 0000-0002-5575-4657 AD - Department of Otolaryngology Head and Neck Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China. yt7065@csu.edu.cn. LA - eng PT - Journal Article DEP - 20231010 PL - United States TA - Cell Death Discov JT - Cell death discovery JID - 101665035 PMC - PMC10564923 COIS- The authors declare no competing interests. EDAT- 2023/10/11 00:42 MHDA- 2023/10/11 00:43 PMCR- 2023/10/10 CRDT- 2023/10/10 23:18 PHST- 2023/07/28 00:00 [received] PHST- 2023/09/28 00:00 [accepted] PHST- 2023/09/22 00:00 [revised] PHST- 2023/10/11 00:43 [medline] PHST- 2023/10/11 00:42 [pubmed] PHST- 2023/10/10 23:18 [entrez] PHST- 2023/10/10 00:00 [pmc-release] AID - 10.1038/s41420-023-01669-7 [pii] AID - 1669 [pii] AID - 10.1038/s41420-023-01669-7 [doi] PST - epublish SO - Cell Death Discov. 2023 Oct 10;9(1):371. doi: 10.1038/s41420-023-01669-7.