期刊
MOLECULAR GENETICS & GENOMIC MEDICINE
卷 8, 期 2, 页码 -出版社
WILEY
DOI: 10.1002/mgg3.999
关键词
biomarker; ceRNA; circular RNA; microRNA; NSCLC; proliferation
资金
- Henan Province Science and Technology Tackling Project [201702259]
Background It is well recognized that competing endogenous RNA (ceRNA) regulatory network is linked to the development and progression of cancer, including non-small cell lung cancer (NSCLC). Herein, we aimed to explore the functional role of circ-CMPK1/miR-302e/cyclin D1 ceRNA signaling in NSCLC. Methods GEO database () was utilized to screen differentially expressed miRNAs in NSCLC. Quantitative reverse transcription PCR (qRT-PCR) and western blotting assays were used to determine gene expression. Cell proliferation analysis was performed with Cell Counting Kit-8 (CCK-8) and cell cycle assays. Luciferase reporter and RNA pull-down assays were conducted to identify the interaction among circ-CMPK1, miR-302e, and cyclin D1. Xenograft tumor model was established to evaluate the role of circ-CMPK1/miR-302e/cyclin D1 axis in vivo. Results miR-302e expression was significantly down-regulated in NSCLC cell lines and tissues and its decrease was closely associated with aggressive clinicopathological features and unfavorable outcome. Overexpression and knockdown of miR-302e obviously retarded and enhanced the growth of NSCLC, respectively. Furthermore, we found that miR-302 was sponged by circular RNA CMPK1 (circ-CMPK1, hsa_circ_0012384), which was remarkably up-regulated in NSCLC and predicted poor prognosis. Circ-CMPK1 was capable to promote NSCLC cells proliferation by increasing the expression of cyclin D1 via inhibiting miR-302 activity. Moreover the miR-302e-mediated tumor inhibition could be effectively counteracted by ectopic expression of circ-CMPK1 or cyclin D1 both in vitro and in vivo. Conclusion Our data demonstrate for the first time that circ-CMPK1/miR-302e/cyclin D1 signaling plays an essential regulatory role in NSCLC and targeting this axis may be an efficacious avenue for treatment of NSCLC patients.
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