Abstract
Circular RNAs (circRNAs), a group of non-coding RNAs, play an important role in cancer biology, and in the present study, we aimed to clarify the expression profiles and biological functions of circRNA circVANGL1 in non-small cell lung cancer (NSCLC). The results showed that circVANGL1 was overexpressed in human NSCLC tissues and cell lines. circVANGL1 expression was closely associated with tumor size, TNM stage and overall survival of NSCLC patients. Further loss-of-function analysis revealed that knockdown of circVANGL1 inhibited proliferation and induced apoptosis in NSCLC cell lines. The migration and invasion of NSCLC cells were also suppressed by circVANGL1 knockdown. In addition, we predicted that circVANGL1 might serve as a competing endogenous RNA (ceRNA), becoming a sink for miR-195, thereby modulating the expression of Bcl-2 in NSCLC cells. Rescue experiments demonstrated that miR-195 inhibitor abrogated the beneficial role of circVANGL1 knockdown in NSCLC cells. Taken together, we conclude that circVANGL1 functions as an oncogene to promote NSCLC progression partly through miR-195/Bcl-2 axis, which might be a novel therapeutic target for NSCLC patients.
Highlights
IntroductionNon-small cell lung cancer (NSCLC), accounting for 85% of all cases, is the most prevalent histological type of lung cancer [1]
Lung cancer is the most commonly occurring cancer around the world
We explored whether circVANGL1 could act as a competing endogenous RNA of miRNAs in Non-small cell lung cancer (NSCLC), and through the Starbase database, the potential binding sites of miR-195 were identified in the circVANGL1 sequence (Figure 4A)
Summary
Non-small cell lung cancer (NSCLC), accounting for 85% of all cases, is the most prevalent histological type of lung cancer [1]. Patients with advanced NSCLC have an average 5-year survival rate of approximately 15% [2]. It is worthy and important for us to further identify genetic regulatory networks involved in NSCLC progression. Circular RNAs (circRNAs), a novel group of endogenous non-coding RNAs, are featured by their covalently closed loop structures without a 5 cap or a 3 Poly A tail [3]. CircRNAs are widely expressed in mammals with cell-type, tissue and developmental phase-specific manner [4]. A novel circRNA, termed as circVANGL1, was identified as an oncogene in bladder cancer [6]. We aimed to clarify the expression profiles and biological functions of circRNA circVANGL1 in NSCLC. We believe that our findings might provide new strategies for diagnosis and treatment against this fatal malignancy
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