Mechanistic study of LncRNA UCA1 promoting growth and cisplatin resistance in lung adenocarcinoma

Abstract Background: The main objective of the current research was to explore the mechanism of LncRNA UCA1 promoting cisplatin resistance in lung adenocarcinoma (LUAD).Method: The UCA1 expression level of LUAD cell lines was herein detected by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). We overexpressed UCA1 in A549 cell and downregulated UCA1 in A549/DDP cell by lentivirus‑mediated technique. We analyzed their biological differences by cell function experiments, RNA pulldown, protein mass spectrometry (MS), and RNA immunoprecipitation technique (RIP). Tumor formation in nude mice was used to investigate the effect of UCA1 on the proliferation and cisplatin sensitivity of A549/DDP in vivo.Result: The results revealed that a higher expression level of UCA1 was expressed in the A549/DDP cell and LUAD tissues than that in A549 cell and adjacent cancer tissues. UCA1 was significantly associated with M stage and clinical stage of LUAD patients from The Cancer Genome Atlas (TCGA) database. Patients with high UCA1 expression had a shorter survival time. After UCA1 overexpressed, the cells capability of proliferation, migration, invasion, clone formation, cisplatin resistance, and the expression level of proteins related to proliferation and drug resistance PCNA, ERCC1 were enhanced, while these trends were mostly reversed in the cells knockdown with UCA1 expression. Tumorigenic assays in nude mice showed that knockdown of UCA1 significantly inhibited tumor growth and reduced cisplatin resistance. It confirmed Enolase 1 (ENO1) was one of RNA binding protein of UCA1.Conclusion: Based on these results, we concluded that UCA1 promoted LUAD progression and cisplatin resistance by binding ENO1 and UCA1 could be a potential diagnostic marker and therapeutic target of LUAD patients.