Abstract
AimThis study aimed to explore the mechanism of LncRNA urothelial carcinoma-associated 1 (UCA1) promoting cisplatin resistance in lung adenocarcinoma (LUAD).MethodThe UCA1 expression level in LUAD cell lines was detected by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). We overexpressed UCA1 in A549 cells and downregulated UCA1 in A549/DDP cells by the lentivirus‑mediated technique. Subsequently, in vitro, and in vivo functional experiments were performed to investigate the functional roles of UCA1 in the growth and metastasis of LUAD cell lines. Furthermore, RNA pulldown, mass spectrometry, and RNA immunoprecipitation technique were performed to analyze various downstream target factors regulated by UCA1.ResultsThe results revealed a higher UCA1 expression level in A549/DDP cells and LUAD tissues than in A549 cells and adjacent cancer tissues. UCA1 expression was significantly associated with distant metastasis, clinical stage, and survival time of patients with LUAD. UCA1 overexpression significantly increased the proliferation, invasion, clone formation, and cisplatin resistance ability and enhanced the expression levels of proliferating cell nuclear antigen and excision repair cross-complementing gene 1 in A549 cells. However, these trends were mostly reversed after the knockdown of UCA1 in A549/DDP cells. Tumorigenic assays in nude mice showed that UCA1 knockdown significantly inhibited tumor growth and reduced cisplatin resistance. Enolase 1 was the RNA-binding protein (RBP) of UCA1.ConclusionBased on the results, we concluded that UCA1 promoted LUAD progression and cisplatin resistance and hence could be a potential diagnostic marker and therapeutic target in patients with LUAD.
Highlights
Lung cancer was the second most diagnosed cancer and the leading cause of cancer death, with an estimated 2.2 million new cancer cases and 1.8 million deaths in 2020 [1]
urothelial carcinoma-associated 1 (UCA1) expression was significantly associated with distant metastasis, clinical stage, and survival time of patients with Lung adenocarcinoma (LUAD)
Tumorigenic assays in nude mice showed that UCA1 knockdown significantly inhibited tumor growth and reduced cisplatin resistance
Summary
Lung cancer was the second most diagnosed cancer and the leading cause of cancer death, with an estimated 2.2 million new cancer cases and 1.8 million deaths in 2020 [1]. The current 5-year survival rate of patients with lung cancer was lower than 20% due to the absence of validity for diagnosis in the early stage and the lack of effective therapies for advanced lung cancer, [2]. Lung adenocarcinoma (LUAD) was the most common histological type of non-small cell lung cancer (NSCLC). Platinum-based chemotherapy was still the first-line treatment for advanced NSCLC and an efficient method to improve the survival rate and life quality of patients [3]. The mechanism of resistance to cisplatin (DDP) was extremely complex, involving multiple genes, and was currently thought to be achieved primarily through multiple mechanisms [5,6,7]. Despite many advances in genomic and proteomic studies, the mechanism of cisplatin resistance remained elusive
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.