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.
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.
Methods
GEO database (GSE102287) 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.