Overexpressed CDR1as functions as an oncogene to promote the tumor progression via miR-7 in non-small-cell lung cancer
Authors Zhang X, Yang D, Wei Y
Received 28 November 2017
Accepted for publication 7 March 2018
Published 10 July 2018 Volume 2018:11 Pages 3979—3987
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Colin Mak
Peer reviewer comments 2
Editor who approved publication: Dr Yao Dai
Xiaofei Zhang,1,* Danfen Yang,2,* Yaqiang Wei1
1Department of Oncology & The Division of Respiratory Medicine, Yan’an People’s Hospital, Yan’an City, People’s Republic of China; 2Department of Medicine, The Division of Respiratory Medicine, Affiliated Hospital of Yan’an University, Yan’an City, People’s Republic of China
*These authors contributed equally to this work
Background: Circular RNA (circRNA) is a novel member of the noncoding RNA and function as efficient microRNA sponges with gene-regulatory potential, especially the circular RNA ciRS-7 (CDR1as)/tumor suppressor miRNA-7 (miR-7) signals. However, the function of CDR1as/miR-7 in non-small cell lung cancer (NSCLC) is unknown.
Methods: Normal lung tissues (n=20), adjacent non-tumor tissues (n=60), and NSCLC tissues (n=60) were collected to determine the expression and significance of CDR1as/miR-7. Lung cancer cell lines A549 and H460 were overexpressed or knocked down of CDR1as, miR-7 to determine the tumor growth etc. The CDR1as/miR-7-related pathway were analyzed.
Results: CDR1as levels was robustly increased with the development of NSCLC (P<0.001) and the NSCLC tissues harbored highest expression of CDR1as, which negatively correlated to the expression of miR-7. Patients with high expression of CDR1as had high TNM stage (P=0.004), more lymph nodes metastasis (LNM) (P=0.021) and shorted overall survival time (OS) (P=0.0135). The CDR1as level was an independent prognostic factor for the patients with NSCLC. Overexpression of CDR1as induced increased cell vitalities and growth, which could be abrogated by knockdown of CDR1as or overexpressed miR-7 to induce apoptosis and G1/S arrest. Mechanistically, CDR1as functioned as miR-7 sponges to up-regulate the key target genes of miR-7 including EGFR, CCNE1 and PIK3CD. The results in vivo further confirmed that CDR1as functioned as oncogene to inhibit the anti-tumor effects of tumor suppressor miR-7 by up-regulation of proliferation index Ki-67, EGFR, CCNE1 and PIK3CD levels.
Conclusion: Overexpressed CDR1as in NSCLC functions promotes the tumor progression via miR-7 signals.
Keywords: CDR1as, miR-7, prognosis, tumor growth, NSCLC
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