环状DENND4C通过上调BRD4信号通路促进肺癌的增殖和转移。

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

作者信息

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

机构信息

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

出版信息

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

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.

目的

探讨环状DENND4C（circDENND4C）对肺癌恶性生物学行为及其下游靶基因和分子机制的影响。

方法

检测circDENND4C在肺癌组织和细胞中的表达。转染沉默circDENND4C后，采用qRT-PCR检测肺癌细胞中circDENND4C、miR-141-3p和BRD4的表达水平。验证circDENND4C与miR-141-3p以及miR-141-3p与BRD4之间的靶向关系。通过CCK-8和EdU检测法检测细胞活性。采用Transwell检测法检测各组A549和NCI-H1299细胞的侵袭能力。研究circDENND4C对裸鼠肺癌增殖和转移的影响。

结果

体外和体内实验结果表明，沉默circDENND4C可降低肺癌细胞的增殖、侵袭和转移能力。机制研究表明，circDENND4C与miR-141-3p存在靶向关系。然而，miR-141-3p与BRD4存在靶向关系。circDENND4C通过海绵吸附miR-141-3p间接上调BRD4，从而促进非小细胞肺癌的转移和增殖。