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

Authors :
Jiali Fu
Jingjing Pan
Xiang Yang
Yan Zhang
Fanggui Shao
Jie Chen
Kate Huang
Yumin Wang
Source :
Cancer Cell International, Vol 21, Iss 1, Pp 1-17 (2021)
Publication Year :
2021
Publisher :
BMC, 2021.

Abstract

Abstract Aim This study aimed to explore the mechanism of LncRNA urothelial carcinoma-associated 1 (UCA1) promoting cisplatin resistance in lung adenocarcinoma (LUAD). Method The 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. Results The 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. Conclusion Based 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.

Details

Language :
English
ISSN :
14752867
Volume :
21
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Cancer Cell International
Publication Type :
Academic Journal
Accession number :
edsdoj.7293d7cc201e4d4086add170c56673eb
Document Type :
article
Full Text :
https://doi.org/10.1186/s12935-021-02207-0