CircDENND4C Promotes Proliferation and Metastasis of Lung Cancer by Upregulating BRD4 Signaling Pathway.

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

doi:10.1155/2021/2469691

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.

Highlights

ObjectiveTo investigate the effects of circDENND4C on the malignant biological behavior of lung cancer and its downstream target genes and molecular mechanisms
With the development of social economy and environmental pollution, the incidence of various cancers and lung-related diseases has increased significantly [1]
Mechanism studies showed that circDENND4C, as an oncogene, upregulated the expression of BRD4 by inhibiting miR-141-3p, promoting the proliferation, invasion, and EMT process of non-small cell lung cancer (NSCLC) cells (Figure 6(f ))

Summary

Objective

To investigate the effects of circDENND4C on the malignant biological behavior of lung cancer and its downstream target genes and molecular mechanisms. E 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. E targeting relationship between circDENND4C and miR-141-3p as well as miR-141-3p and BRD4 was verified. Effects of circDENND4C on proliferation and metastasis of lung cancer in nude mice were studied. 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. MiR141-3p has a targeting relationship with BRD4. CircDENND4C indirectly upregulated BRD4 through sponge adsorption of miR141-3p, thereby promoting metastasis and proliferation of NSCLC. CircDENND4C, as an oncogene, promotes the proliferation, invasion, and metastasis of lung cancer cells Conclusion. circDENND4C, as an oncogene, promotes the proliferation, invasion, and metastasis of lung cancer cells

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