lncRNA LIFR-AS1 suppresses invasion and metastasis of non-small cell lung cancer via the miR-942-5p/ZNF471 axis

Qun Wang; Jing Wu; Hui Huang; Yan Jiang; Ying Huang; Hongyan Fang; Gang Zheng; Xiaochun Zhou; Yujuan Wu; Changjiang Lei; Desheng Hu

doi:10.1186/s12935-020-01228-5

lncRNA LIFR-AS1 suppresses invasion and metastasis of non-small cell lung cancer via the miR-942-5p/ZNF471 axis

Cancer Cell Int. 2020 May 24:20:180. doi: 10.1186/s12935-020-01228-5. eCollection 2020.

Authors

Qun Wang^#^{1

2

3}, Jing Wu^#², Hui Huang^#², Yan Jiang⁴, Ying Huang², Hongyan Fang², Gang Zheng⁵, Xiaochun Zhou², Yujuan Wu², Changjiang Lei⁵, Desheng Hu¹

Affiliations

¹ Department of Radiotherapy, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, 116 Zhuodaoquan South Road, Wuhan, 430070 China.
² Department of Oncology, The Fifth Hospital of Wuhan, Wuhan, China.
³ WuHan University, Wuhan, China.
⁴ Department of Pneumology, The Fifth Hospital of Wuhan, Wuhan, China.
⁵ Department of General Surgery, The Fifth Hospital of Wuhan, Wuhan, China.

^# Contributed equally.

Abstract

Background: MicroRNA 942-5p (miR-942-5p) has been reported to promote migration and invasion in non-small cell lung cancer (NSCLC), but the underlying mechanism is not completely understood. The interplay between long non-coding RNAs (lncRNAs) and miRNAs plays a crucial role in tumor progression.

Methods: In the present study, we performed bioinformatic and biochemical analyses to identify miR-942-5p-interacting lncRNAs. The function and clinical significance of the candidate lncRNA(s) in NSCLC were determined.

Results: We identified LIFR-AS1 as a pivotal miR-942-5p-interacting lncRNA. Overexpression of miR-942-5p caused a reduction of LIFR-AS1 in NSCLC cells. LIFR-AS1 showed the ability to sponge miR-942-5p, leading to derepression of ZNF471. Functionally, LIFR-AS1 overexpression inhibited NSCLC cell migration and invasion, whereas LIFR-AS1 silencing yielded an opposite effect. In vivo studies confirmed that LIFR-AS1 overexpression suppressed lung metastasis of NSCLC cells. Rescue experiments demonstrated that enforced expression of miR-942-5p or depletion of ZNF471 restored the migration and invasion capacity of LIFR-AS1-overexpressing cells. Moreover, overexpression of ZNF471 restrained NSCLC cell invasion. Clinically, LIFR-AS1 downregulation was significantly correlated with TNM stage, lymph node metastasis, and reduced overall survival in NSCLC patients.

Conclusions: we provide first evidence for the involvement of the LIFR-AS1/miR-942-5p/ZNF471 axis in NSCLC invasion and metastasis. LIFR-AS1 may represent a novel target for the treatment of NSCLC.

Keywords: Lung cancer; Metastasis; Target gene; lncRNA; miR-942-5p.