Abstract
CircRNAs could play critical functions in tumor progression. However, the expression and underlying mechanism of circRNAs in lung cancer progression remain poorly defined. In the present study, high-throughput microarray assay revealed that hsa_circRNA_100833 (identified as circFADS2) was markedly evaluated in lung cancer tissues, and it was further validated by qRT-PCR. High expression of circFADS2 was correlated with advanced TNM stage, lymph node metastasis, poor differentiation, and shorter overall survival of NSCLC patients. In vitro assays results showed that circFADS2 inhibition suppressed lung cancer cells proliferation and invasion ability. Bioinformatics analysis showed that miR-498 contained the complementary binding region of circFADS2, which was confirmed by Dual-luciferase reporter assay. In addition, the expression of miR-498 was down-regulated and negatively associated with circFADS2 expression in nonsmall cell lung cancer. Furthermore, rescue assays showed that miR-498 inhibitors abolished the effects of circFADS2 inhibition on lung cancer cells progression. Taken together, our findings indicated that circFADS2 was an effective tumor promoter in lung cancer progression, and its functions were performed by regulating the expression of miR-498. These data suggested that circFADS2 could act as a target for lung cancer treatment.
Highlights
Lung cancer is the leading cause of cancer related death both in men and women worldwide with more than 80% of lung cancer being classified as nonsmall cell lung cancer (NSCLC) [1,2]
It is of great importance to uncover the molecular mechanism of cancer cells proliferation and metastasis in NSCLC to facilitate the developments of new drugs
The expression levels of circFADS2 were further confirmed in another 43 paired NSCLC tissues. qRT-PCR results showed that the expression of circFADS2 was markedly increased in NSCLC tissues (Figure 1D; P
Summary
Lung cancer is the leading cause of cancer related death both in men and women worldwide with more than 80% of lung cancer being classified as nonsmall cell lung cancer (NSCLC) [1,2]. It is of great importance to uncover the molecular mechanism of cancer cells proliferation and metastasis in NSCLC to facilitate the developments of new drugs. Increasing evidence showed that circRNAs could play important roles in many biological processes, such as cell proliferation, invasion, and differentiation [7,8]. Zong et al showed that circRNA 102231 was increased and could act as a potential biomarker and therapeutic target for lung cancer patients [9]. Jiang et al [10] indicated that circular RNA hsa circ 0007385 could function as an oncogene in nonsmall cell lung cancer tumorigenesis. Wan et al [11] indicated that circular RNA-ITCH suppressed lung cancer proliferation via inhibiting the Wnt/β-catenin pathway
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