DLX6-AS1 activated by H3K4me1 enhanced secondary cisplatin resistance of lung squamous cell carcinoma through modulating miR-181a-5p/miR-382-5p/CELF1 axis

• Published in: Scientific reports Vol. 11; no. 1; p. 21014
• Main Authors: Zhao, Xu, Wang, Jizhao, Zhu, Rui, Zhang, Jing, Zhang, Yunfeng
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 25.10.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/67; 631/67/1612; 631/67/1612/1350; Apoptosis; Apoptosis - genetics; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - metabolism; CELF1 Protein - genetics; Cell Line, Tumor; Cell Movement; Cell Proliferation; Chemotherapy; Cholecystokinin; Cisplatin; Drug Resistance, Neoplasm - genetics; Flow cytometry; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Histones - metabolism; Homeodomain Proteins - genetics; Humanities and Social Sciences; Humans; Lung cancer; Lung carcinoma; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; MicroRNAs - genetics; multidisciplinary; Non-small cell lung carcinoma; Reporter gene; RNA Interference; RNA, Long Noncoding - genetics; Science; Science (multidisciplinary); Small cell lung carcinoma; Squamous cell carcinoma
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-99555-8

Cisplatin (CDDP) based chemotherapy is widely used as the first-line strategy in treating non-small cell lung cancer (NSCLC), especially lung squamous cell carcinoma (LUSC). However, secondary cisplatin resistance majorly undermines the cisplatin efficacy leading to a worse prognosis. In this respect, we have identified the role of the DLX6-AS1/miR-181a-5p/miR-382-5p/CELF1 axis in regulating cisplatin resistance of LUSC. qRT-PCR and Western blot analysis were applied to detect gene expression. Transwell assay was used to evaluate the migration and invasion ability of LUSC cells. CCK-8 assay was used to investigate the IC50 of LUSC cells. Flow cytometry was used to test cell apoptosis rate. RNA pull-down and Dual luciferase reporter gene assay were performed to evaluate the crosstalk. DLX6-AS1 was aberrantly high expressed in LUSC tissues and cell lines, and negatively correlated with miR-181a-5p and miR-382-5p expression. DLX6-AS1 expression was enhanced by H3K4me1 in cisplatin resistant LUSC cells. Besides, DLX6-AS1 knockdown led to impaired IC50 of cisplatin resistant LUSC cells. Furthermore, DLX6-AS1 interacted with miR-181a-5p and miR-382-5p to regulate CELF1 expression and thereby mediated the cisplatin sensitivity of cisplatin resistant LUSC cells. DLX6-AS1 induced by H3K4me1 played an important role in promoting secondary cisplatin resistance of LUSC through regulating the miR-181a-5p/miR-382-5p/CELF1 axis. Therefore, targeting DLX6-AS1 might be a novel way of reversing secondary cisplatin resistance in LUSC.