Circular RNA circ‐CMPK1 contributes to cell proliferation of non‐small cell lung cancer by elevating cyclin D1 via sponging miR‐302e

Abstract

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 (GSE10 2287) 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. K E Y W O R D Sbiomarker, ceRNA, circular RNA, microRNA, NSCLC, proliferation 2 of 10 | CUI et al.

Value of circular RNA 0007385 in disease monitoring and prognosis estimation in non–small‐cell lung cancer patients

“…A recent study shows that circ-CMPK1 promotes NSCLC cancer cell proliferation through increasing cyclin D1 expression by acting as a sponge of miR-302e. 20 Another study reports that circ- a newly discovered circRNA in 2018, we did not find more studies about the role of hsa_circ_0007385 in NSCLC or in other disease. 14 In addition, the molecular mechanisms about the regulatory role of hsa_circ_0007385 in NSCLC were not investigated in this study, which was due to that there has been a previous study illustrating the effect of hsa_circ_0007385 on NSCLC cell functions, and the major aim of this study was to assess the clinical value of hsa_circ_0007385 in NSCLC.…”

“…In the last two decades, there have been more and more mode‐of‐action studies revealing the functions of circRNAs in NSCLC. A recent study shows that circ‐CMPK1 promotes NSCLC cancer cell proliferation through increasing cyclin D1 expression by acting as a sponge of miR‐302e 20 . Another study reports that circ‐FGFR1 overexpression enhances migration, invasion, proliferation and immune evasion in vitro as well as promotes resistance to anti‐PD‐1 treatment in vivo in NSCLC 21 .…”

Circular RNA circ_0000284 plays an oncogenic role in the progression of non-small cell lung cancer through the miR-377-3p-mediated PD-L1 promotion

“…Chen et al alleged that circ_100290 improved cell growth and glycolysis of oral squamous cell carcinoma by acting as a ceRNA for miR-378a to relieve the inhibition of GLUT1 [34]. And the circ-CMPK1/ miR-302e/cyclin D1 axis was disclosed in NSCLC [35]. Herein, circ_0000284 was shown to counteract the miR-377-3p-mediated PD-L1 suppression, consequently increasing the expression of PD-L1, which further caused the progression of NSCLC.…”

CircHIPK3/miR-381-3p axis modulates proliferation, migration, and glycolysis of lung cancer cells by regulating the AKT/mTOR signaling pathway

“…Dysregulated circRNAs have been manifested to be closely related to the proliferation and metastasis of non-small cell lung cancer (NSCLC) cells and have the potential to be diagnostic biomarkers of lung cancer [ 4 , 5 ]. For instance, circCMPK1 (hsa_circ_0012384) positively modulated cell proliferation of NSCLC cells by increasing cyclin D1 expression by sponging miR-302e [ 6 ]. Li et al reported that circ_0000003 could accelerate the progression of NSCLC by promoting the proliferation and metastasis via the miR-338-3p/IRS2 pathway [ 7 ].…”