MCF2L-AS1/miR-874-3p/STAT3 feedback loop contributes to lung adenocarcinoma cell growth and cisplatin resistance

• Published in: Heliyon Vol. 9; no. 11; p. e21342
• Main Authors: Xu, Min, Zheng, Jing, Wang, Jun, Huang, Haitao, Hu, Gang, He, Hailan
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.11.2023; Elsevier
• Subjects: Cisplatin resistance; Lung adenocarcinoma; MCF2L-AS1; miR-874-3p; STAT3; miR-874-3p; MCF2L-AS1; Cisplatin resistance; Lung adenocarcinoma; STAT3
• ISSN: 2405-8440; 2405-8440
• DOI: 10.1016/j.heliyon.2023.e21342

Long noncoding RNA (lncRNA) is widely acknowledged for its crucial role in the biological processes of various human cancers. MCF2L antisense RNA 1 (MCF2L-AS1) is a newly identified lncRNA, which remains unexplored in the context of cancer. MCF2L-AS1 expression was examined using qRT-PCR analysis. The impact of MCF2L-AS1 on LUAD cell growth was assessed through CCK-8, colony formation, EdU, caspase-3 activity, TUNEL, Western blot, and transwell assays. The interaction between miR-874-3p and MCF2L-AS1 or STAT3 was confirmed by RIP, luciferase reporter, and RNA pull-down assays. Our study demonstrated the overexpression of MCF2L-AS1 in LUAD cells. Functionally, the silencing of MCF2L-AS1 hindered cell proliferation, migration, and invasion, while promoting cell apoptosis. Notably, the depletion of MCF2L-AS1 was associated with decreased cisplatin resistance. Mechanistically, MCF2L-AS1 was identified as an upstream gene of miR-874-3p, negatively regulating its expression. Following this, STAT3, the downstream target of miR-874-3p, was identified. Additionally, the expression of STAT3 was inversely related to miR-874-3p and positively regulated by MCF2L-AS1. A restoration assay suggested that MCF2L-AS1 promoted LUAD cell growth by sponging miR-874-3p and modulating STAT3 expression. Intriguingly, STAT3 was subsequently confirmed as a transcription factor that binds to the MCF2L-AS1 promoter, thereby enhancing its transcription. The MCF2L-AS1/miR-874-3p/STAT3 feedback loop plays a significant role in LUAD cell growth and cisplatin resistance.