circRACGAP1 Promotes Proliferation of Non-Small Cell Lung Cancer Cells through the miR-1296/CDK2 Pathway

Zhao, Yang; Deng, Liyong; Xie, Yi; Wang, Weiming; Chai, Qin; Wang, Guihua

doi:10.14712/fb2024070020104

Folia Biologica > Archive > 2024, Vol. 70 > Issue 2 > circRACGAP1 Promotes Proliferation of…

Fol. Biol. 2024, 70, 104-112

https://doi.org/10.14712/fb2024070020104

circRACGAP1 Promotes Proliferation of Non-Small Cell Lung Cancer Cells through the miR-1296/CDK2 Pathway

Yang Zhao, Liyong Deng, Yi Xie, Weiming Wang, Qin Chai, Guihua Wang

The Affiliated Changsha Central Hospital, Department of Oncology, Hengyang Medical School, University of South China, Changsha, Hunan, China

Received June 2023
Accepted May 2024

Circular RNAs (circRNAs) have played an essential role in cancer development. This study aimed to illustrate the impact and potential mechanism of circRACGAP1 action in NSCLC development. The expression patterns of circRACGAP1, miR-1296, and CDK2 in NSCLC tissues and cell lines were analysed by RT-qPCR. The function of circRACGAP1 in NSCLC cell proliferation and apoptosis was investigated using the CCK-8 assay, flow cytometry, TUNEL staining, and Western blot. The interaction among circRACGAP1, miR-1296, and CDK2 was clarified by dual-luciferase reporter assay while the correlation was confirmed by the Pearson correlation coefficient. The expression of circRACGAP1 and CDK2 was up-regulated in NSCLC tissues, while the expression of miR-1296 was down-regulated. Cell function studies further revealed that circRACGAP1 could promote NSCLC cell proliferation, accelerate the cell cycle process, up-regulate B-cell lymphoma 2 (Bcl2) expression, and down-regulate Bcl2-associated X (Bax) expression. miR-1296 was identified as a downstream target to reverse circRACGAP1-mediated cell proliferation. miR-1296 directly targeted the 3’-UTR of CDK2 to regulate proliferation and apoptosis of NSCLC cells. Additionally, the dual-luciferase reporter assay and Pearson correlation coefficient analysis proved that circRACGAP1 acted in NSCLC cells by negatively regulating miR-1296 expression and positively regulating CDK2 expression. In summary, our study revealed that circRACGAP1 promoted NSCLC cell proliferation by regulating the miR-1296/CDK2 pathway, providing potential diagnostic and therapeutic targets for NSCLC.

Keywords

NSCLC, circRACGAP1, miR-1296, CDK2, proliferation.

Funding

This study was supported by the Natural Science Foundation of Changsha City (kq2014025) and the Key Project Foundation of Hunan Provincial Health Commission (KJZX2021019).