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Circ-PITX1 Promotes the Progression of Non-Small Cell Lung Cancer Through Regulating the miR-1248/CCND2 Axis

Authors Yue Q, Xu Y, Deng X, Wang S, Qiu J, Qian B, Zhang Y

Received 14 October 2020

Accepted for publication 28 January 2021

Published 9 March 2021 Volume 2021:14 Pages 1807—1819

DOI https://doi.org/10.2147/OTT.S286820

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Sanjay Singh


Qianyu Yue,* Yanyan Xu,* Xiaoli Deng, Shenglan Wang, Jingman Qiu, Baojiang Qian, Yunhui Zhang

Department of Pulmonary and Critical Care Medicine, The First People’s Hospital of Yunnan Province (The Affiliated Hospital of Kunming University of Science and Technology), Kunming, 650032, Yunnan, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Yunhui Zhang; Xiaoli Deng
Department of Pulmonary and Critical Care Medicine, The First People’s Hospital of Yunnan Province (The Affiliated Hospital of Kunming University of Science and Technology), No. 157, Jinbi Road, Kunming, 650032, Yunnan, People’s Republic of China
Tel +86 871-63638515
Email [email protected]; [email protected]

Background: Circular RNA (circRNA) is a key regulator of cancer, and it has been proved to be involved in the regulation of cancer progression including non-small cell lung cancer (NSCLC). Circ-PITX1 was found to be a significantly upregulated circRNA in NSCLC, and its role and potential mechanism in NSCLC progression deserve further investigation.
Methods: The expression levels of circ-PITX1, microRNA (miR)-1248 and cyclin D2 (CCND2) were examined by quantitative real-time PCR (qRT-PCR). Cell proliferation, apoptosis, cell cycle process, migration and invasion were determined using cell counting kit 8 (CCK8) assay, colony formation assay, flow cytometry, wound healing assay and transwell assay. Xenograft models were built to explore the role of circ-PITX1 in NSCLC tumor growth in vivo. The glycolysis and glutamine metabolism of cells were assessed by detecting the consumptions of glucose and glutamine, cell extracellular acidification rate (ECAR), and the productions of lactate, α-ketoglutaric acid (α-KG) and ATP. The protein levels of hexokinase 2 (HK-2), glutaminase 1 (GLS1) and CCND2 were tested by Western blot (WB) analysis. Dual-luciferase reporter assay and RIP assay were employed to verify the interaction between miR-1248 and circ-PITX1 or CCND2.
Results: Circ-PITX1 was upregulated in NSCLC and its silencing could inhibit the proliferation, migration, invasion, cell cycle process, glycolysis, glutamine metabolism, and promote the apoptosis of NSCLC cells in vitro, as well as reduced tumor growth in vivo. In the terms of mechanism, we found that circ-PITX1 could act as a sponge of miR-1248, and miR-1248 could target CCND2. In addition, miR-1248 inhibitor reversed the inhibitory effect of circ-PITX1 knockdown on NSCLC progression. Similarly, CCND2 overexpression also reversed the suppressive effect of miR-1248 on NSCLC progression. Moreover, circ-PITX1 positively regulated CCND2 expression by sponging miR-1248.
Conclusion: Circ-PITX1 served as a sponge of miR-1248 to promote NSCLC progression by upregulating CCND2.

Keywords: non-small cell lung cancer, circ-PITX1, miR-1248, CCND2

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