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

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 (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. 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.

A regulatory circuit of circ-MTO1/miR-17/QKI-5 inhibits the proliferation of lung adenocarcinoma.

Circular RNA (circRNA) is a new class of non-coding RNA that plays a pivotal role in carcinogenesis. Recently, circ-MTO1 (hsa_circ_0007874) was shown to be a cancer-related circRNA. However, its role in lung adenocarcinoma (LUAD) has not been reported. Here, we found that circ-MTO1 was significantly down-regulated in LUAD, which was closely associated with malignant features and dismal prognosis. Enforced expression of circ-MTO1 suppressed the growth of LUAD cells both in vitro and in vivo. Subsequent mechanism experiments showed that circ-MTO1 served as a sponge of oncogenic miR-17 to increase the expression of RNA-binding protein QKI-5, leading to the inactivation of Notch signaling pathway, thereby restraining the growth of LUAD. Importantly, increased QKI-5 expression caused by circ-MTO1 overexpression in turn promoted circ-MTO1 expression. Clinically, circ-MTO1 expression was strongly positively correlated with QKI-5 expression, but negatively correlated with miR-17 expression. Taken together, our data suggest that circ-MTO1 is a critical negative regulator of LUAD and elucidate the potential molecular mechanism of a novel circ-MTO1/miR-17/QKI-5 feedback loop in inhibiting LUAD progression.