Long non-coding RNA SLC25A25-AS1 exhibits oncogenic roles in non-small cell lung cancer by regulating the microRNA-195-5p/ITGA2 axis

被引:15
|
作者
Chen, Jinqin [1 ]
Gao, Chengpeng [2 ]
Zhu, Wei [1 ]
机构
[1] Weifang Peoples Hosp, Dept Chest Surg, 151 Guangwen Rd, Weifang 261401, Shandong, Peoples R China
[2] Weifang Peoples Hosp, Dept Resp Med, Weifang 261401, Shandong, Peoples R China
关键词
non-coding RNA; competitive endogenous RNA; microRNA; lung cancer; COMPETING ENDOGENOUS RNA; THERAPY RESISTANCE; EXPRESSION; LNCRNA; PROLIFERATION; TUMORIGENESIS; PATHOGENESIS; BIOMARKERS; DIAGNOSIS; MICRORNAS;
D O I
10.3892/ol.2021.12790
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Long non-coding RNA SLC25A25 antisense RNA 1 (SLC25A25-AS1) exerts antitumour activity in colorectal cancer. The present study investigated whether SLC25A25-AS1 is implicated in the aggressiveness of non-small cell lung cancer (NSCLC) and the possible underlying mechanism. SLC25A25-AS1 expression in NSCLC was determined by reverse transcription-quantitative PCR. The proliferation, apoptosis, migration and invasion of NSCLC cells were tested in vitro through cell counting kit-8 assay, flow cytometry analysis, Transwell migration and invasion assays, followed by in vivo validation using animal experiments. Additionally, the competitive endogenous RNA theory for SLC25A25-AS1, microRNA-195-5p (miR-195-5p) and integrin alpha 2 (ITGA2) was identified using subcellular fractionation, bioinformatics analysis, reverse transcription-quantitative PCR, western blotting, a luciferase assay and RNA immunoprecipitation. As compared with normal lung tissues, increased expression of SLC25A25-AS1 was demonstrated in NSCLC tissues using The Cancer Genome Atlas database.. In addition, SLC25A25-AS1 was overexpressed in both NSCLC tissues and cell lines. High SLC25A25-AS1 expression was markedly associated with shorter overall survival time of patients with NSCLC. SLC25A25-AS1 silencing impeded NSCLC cell proliferation and triggered apoptosis, while restricting cell migration and invasion. Tumour growth in vivo was also impaired by SLC25A25-AS1 silencing. Mechanistically, SLC25A25-AS1 was demonstrated to be an miR-195-5p sponge in NSCLC cells. miR-195-5p mimics decreased ITGA2 expression in NSCLC cells by directly targeting ITGA2, and SLC25A25-AS1 interference decreased ITGA2 expression by sequestering miR-195-5p. Furthermore, the antitumour effects of SLC25A25-AS1 silencing on malignant behaviours were counteracted when ITGA2 was restored or when miR-195-5p was silenced. In summary, by controlling the miR-195-5p/ITGA2 axis, SLC25A25-AS1 served tumour-promoting roles in NSCLC cells. Therefore, the SLC25A25-AS1/miR-195-5p/ITGA2 signalling pathway might be an attractive target for future therapeutic options in NSCLC.
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页数:13
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