PMID- 37534482 OWN - NLM STAT- Publisher LR - 20231024 IS - 1875-5550 (Electronic) IS - 1389-2037 (Linking) VI - 24 IP - 9 DP - 2023 TI - REST-restrained lncRNA EPB41L4A-AS2 Modulates Laryngeal Squamous Cell Carcinoma Development via Regulating miR-1254/HIPK2 Pathway. PG - 737-757 LID - 10.2174/1389203724666230803094028 [doi] AB - BACKGROUND: LncRNAs have been corroborated to exert crucial effects in malignancies, including laryngeal squamous cell carcinoma (LSCC). Nevertheless, the role and mechanism of EPB41L4A- AS2 in LSCC are inadequately investigated and warrant further exploration. METHODS: Relevant database was adopted to analyze the relationship between EPB41L4A-AS2 expression level and tumors. The expressions and relationships of EPB41L4A-AS2, RE-1 silencing transcription factor (REST), miR-1254, and homeodomain interacting protein kinase 2 (HIPK2) in LSCC cells were evaluated by qRT-PCR, Pearson's correlation tests, RNA immunoprecipitation, RNA pull-down assay, chromatin immunoprecipitation, database, and dual-luciferase reporter assay. Following the required transfection, the biological behaviors of LSCC cells were examined using cell function experiments. Meanwhile, the levels of Ki-67 and apoptosis-, and epithelial-mesenchymal transition (EMT) pathway-related proteins were quantified with Western blot. Moreover, xenografts in nude mice were constructed, and the tumor volume and weight were measured. Ki-67 positivity was determined by immunohistochemical staining. RESULTS: EPB41L4A-AS2 and HIPK2 were lower-expressed, yet miR-1254 and REST were higher- expressed in LSCC cells. Pearson's correlation assay results exhibited a positive correlation between HIPK2 and EPB41L4A-AS2 and a negative correlation between HIPK2 and miR-1254. Overexpressed EPB41L4A-AS2 diminished the biological behavior, and repressed the levels of Ki-67 and EMT-related markers in LSCC cells whilst enhancing those of apoptosis-related markers. These aforementioned effects were counteracted by miR-1254 mimic. Moreover, EPB41L4A- AS2 overexpression suppressed the growth of tumors and reduced the positive expression of Ki-67 in nude mice. Besides, miR-1254 aggravated the biological behaviors and elevated the levels of Ki-67 and EMT-related proteins in LSCC cells while reducing the levels of apoptosis-related markers via targeting HIPK2. CONCLUSION: REST-restrained EPB41L4A-AS2 modulates LSCC development via regulating miR-1254/HIPK2 pathway. CI - Copyright(c) Bentham Science Publishers; For any queries, please email at epub@benthamscience.net. FAU - Yang, Huijun AU - Yang H AD - Department of Otolaryngology, First Affiliated Hospital of China Medical University, No.155, Nanjing North Street, Heping District, Shenyang City, Liaoning Province, 110001, China. FAU - Yu, Gang AU - Yu G AD - Department of Otolaryngology, First Affiliated Hospital of China Medical University, No.155, Nanjing North Street, Heping District, Shenyang City, Liaoning Province, 110001, China. FAU - Wang, Yan AU - Wang Y AD - Department of Otolaryngology, First Affiliated Hospital of China Medical University, No.155, Nanjing North Street, Heping District, Shenyang City, Liaoning Province, 110001, China. FAU - Guo, Xing AU - Guo X AD - Department of Otolaryngology, First Affiliated Hospital of China Medical University, No.155, Nanjing North Street, Heping District, Shenyang City, Liaoning Province, 110001, China. LA - eng PT - Journal Article PL - United Arab Emirates TA - Curr Protein Pept Sci JT - Current protein & peptide science JID - 100960529 SB - IM OTO - NOTNLM OT - EPB41L4A-AS2 OT - Ki-67 OT - RE-1 silencing transcription factor OT - homeodomain-interacting protein kinase 2 OT - laryngeal squamous cell carcinoma OT - miR-1254 EDAT- 2023/08/03 06:43 MHDA- 2023/08/03 06:43 CRDT- 2023/08/03 05:35 PHST- 2023/02/07 00:00 [received] PHST- 2023/05/30 00:00 [revised] PHST- 2023/07/03 00:00 [accepted] PHST- 2023/08/03 06:43 [pubmed] PHST- 2023/08/03 06:43 [medline] PHST- 2023/08/03 05:35 [entrez] AID - CPPS-EPUB-133339 [pii] AID - 10.2174/1389203724666230803094028 [doi] PST - ppublish SO - Curr Protein Pept Sci. 2023;24(9):737-757. doi: 10.2174/1389203724666230803094028.