Downregulation of long non-coding RNA ZXF1 restricts cell survival by targeting miR-634-GRB2 in lung adenocarcinoma

Xubin  Ren; Nie  Xu; Yunting Zhang; Tao  Wang

doi:10.18388/abp.2020_2875

Xubin Ren Department of Respiratory and Critical Medicine, Chengdu First People’s Hospital, Integrated TCM and Western Medicine Hospital affiliated to Chengdu University of TCM, Chengdu City, Sichuan Province, 610000, China
Nie Xu Department of Oncology, Chengdu First People’s Hospital, Integrated TCM and Western Medicine Hospital affiliated to Chengdu University of TCM, Chengdu City, Sichuan Province, 610000, China
Yunting Zhang Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan City, Hubei Province, 430061, China https://orcid.org/0000-0003-2044-3610
Tao Wang Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan City, Hubei Province, 430061, China

DOI: https://doi.org/10.18388/abp.2020_2875

Abstract

Increasing evidence demonstrates that long non-coding RNAs (lncRNAs) play important regulatory roles in mediating initiation and progression of lung adenocarcinoma (LA), which is one of the most lethal in humans. A previous study reported that lncRNAZXF1 was dysregulated in LA and enhanced expression of ZXF1 promoted the invasion and metastasis in LA. However, the effect of ZXF1 on LA progression and its underlying mechanisms were not thoroughly investigated. In our in vitro experiments, qRT-PCR revealed that the expression level of ZXF1 in LA tissues and tumor cells were significantly higher than that in adjacent normal tissues and normal cells. Furthermore, bioinformatics analysis, luciferase reporter assay, western blot and RNA immunoprecipitation (RIP) assay showed that ZXF1 could directly interact with miR-634, which targets GRB2. Therefore, we propose that ZXF1 could function as an oncogene partly by sponging miR-634 and therefore regulating GRB2 expression in LA. Overall, this study demonstrated, for the first time, that the lncRNA ZXF1/miR-634/GRB2 axis plays crucial roles in modulating LA progression. Moreover, lncRNA ZXF1 might potentially improve LA prognosis and serve as a therapeutic target for the treatment of LA.