LncRNA-AC009948.5 promotes invasion and metastasis of lung adenocarcinoma by binding to miR-186-5p

Jun Bai; Hongli Li; Xinlu Chen; Lin Chen; Yaqiong Hu; Lu Liu; Yanqiao Zhao; Wei Zuo; Baogang Zhang; Chonggao Yin

doi:10.3389/fonc.2022.949951

LncRNA-AC009948.5 promotes invasion and metastasis of lung adenocarcinoma by binding to miR-186-5p

Front Oncol. 2022 Aug 19:12:949951. doi: 10.3389/fonc.2022.949951. eCollection 2022.

Authors

Jun Bai¹, Hongli Li², Xinlu Chen¹, Lin Chen¹, Yaqiong Hu¹, Lu Liu¹, Yanqiao Zhao¹, Wei Zuo³, Baogang Zhang¹, Chonggao Yin⁴

Affiliations

¹ Department of Pathology, Weifang Medical University, Weifang, China.
² Experimental Center for Medicine Research, Weifang Medical University, Weifang, China.
³ School of Clinical Medicine, Weifang Medical University, Weifang, China.
⁴ College of Nursing, Weifang Medical University, Weifang, China.

Abstract

Background: Long non-coding RNAs (LncRNAs) has been confirmed to play a crucial role in the development and progression of various cancer types. Here we evaluated the expression profiles of LncRNAs in Lung adenocarcinoma (LUAD) tissues and identified a novel LncRNA, termed LncRNA-AC009948.5. However, the role and potential molecular mechanisms of this novel LncRNA in LUAD carcinogenesis is unknown.

Methods: Regarding the public databases and based on integrating bioinformatics analyses, we determined whether LncRNA-AC009948.5 exerts its oncogenic functions via sponging miR-186-5p in LUAD. Furthermore, we determined whether NCAPG2 was a downstream target of miR-186-5p. Moreover, the expression level and biological function of LncRNA-AC009948.5 in LUAD were determined by qRT-PCR, cell apoptosis, Edu, transwell, wound healing and western blot assays. Besides, xenograft mice were established for validation. We explored the expression of LncRNA-AC009948.5 and its roles in the prognosis of LUAD.

Results: LncRNA expression microarray data indicate that LncRNA-AC009948.5 is upregulated in LUAD samples. The present study confirmed the upregulation of LncRNA-AC009948.5 in LUAD tissues and cells. Encreased expression of LncRNA-AC009948.5 was correlated with tumor size, lymph nodes, distant metastasis and histological grade, and poor prognosis.LncRNA-AC009948.5 knockdown significantly inhibited cell proliferation, migration, and invasion in vitro, as well as tumorigenesis and metastasis in vivo. Conversely, LncRNA-AC009948.5 upregulated had opposite effects. Mechanistically, we elucidated that LncRNA-AC009948.5 could directly bind to miR-186-5p and subsequently suppress expression of the target gene of NCAPG2.

Conclusions: LncRNA-AC009948.5 promotes lung adenocarcinoma cells metastasis via the miR-186-5p/NCAPG2 axis and activation of the EMT process. Which may serve as potential targets for the treatment of LUAD in the future.

Keywords: LncRNA-AC009948.5; epithelial-mesenchymal transition; invasion and metastasis; lung adenocarcinoma; miR-186-5p.