circDENND4C Promotes Proliferation and Metastasis of Lung Cancer by Upregulating BRD4 Signaling Pathway

Dongjie Ma; Yingzhi Qin; Shanqing Li; Li Li; Jia He; Yeye Chen; Xiaoyun Zhou; Hongsheng Liu

doi:10.1155/2021/2469691

circDENND4C Promotes Proliferation and Metastasis of Lung Cancer by Upregulating BRD4 Signaling Pathway

J Oncol. 2021 Nov 28:2021:2469691. doi: 10.1155/2021/2469691. eCollection 2021.

Authors

Dongjie Ma¹, Yingzhi Qin¹, Shanqing Li¹, Li Li¹, Jia He¹, Yeye Chen¹, Xiaoyun Zhou¹, Hongsheng Liu¹

Affiliation

¹ Department of Thoracic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China.

Abstract

Objective: To investigate the effects of circDENND4C on the malignant biological behavior of lung cancer and its downstream target genes and molecular mechanisms.

Methods: The expression of circDENND4C in lung cancer tissues and cells was detected. After transfection with silenced circDENND4C, the expression levels of circDENND4C, miR-141-3p, and BRD4 in lung cancer cells were detected by qRT-PCR. The targeting relationship between circDENND4C and miR-141-3p as well as miR-141-3p and BRD4 was verified. Cell activity was detected by CCK-8 and EdU assay. Transwell assay was used to detect the invasiveness of A549 and NCI-H1299 in each group. Effects of circDENND4C on proliferation and metastasis of lung cancer in nude mice were studied.

Results: In vitro and in vivo results showed that circDENND4C silencing reduced the proliferation, invasion, and metastasis of lung cancer cells. Mechanism studies showed that circDENND4C has a targeting relationship with miR-141-3p. However, miR-141-3p has a targeting relationship with BRD4. circDENND4C indirectly upregulated BRD4 through sponge adsorption of miR-141-3p, thereby promoting metastasis and proliferation of NSCLC.

Conclusion: circDENND4C, as an oncogene, promotes the proliferation, invasion, and metastasis of lung cancer cells.