Int J Biol Sci 2022; 18(10):4151-4170. doi:10.7150/ijbs.72386 This issue Cite

Research Paper

E2F2 promotes lung adenocarcinoma progression through B-Myb- and FOXM1-facilitated core transcription regulatory circuitry

Kailong Du1,2#, Shijie Sun1,2#, Tinghui Jiang1,2#, Tao Liu1,2, Xiaofeng Zuo1,2, Xing Xia1,2, Xianjun Liu1,2, Yitao Wang1,2✉, Youquan Bu1,2✉

1. Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China.
2. Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, China.
# These authors contributed equally to this work.

Citation:
Du K, Sun S, Jiang T, Liu T, Zuo X, Xia X, Liu X, Wang Y, Bu Y. E2F2 promotes lung adenocarcinoma progression through B-Myb- and FOXM1-facilitated core transcription regulatory circuitry. Int J Biol Sci 2022; 18(10):4151-4170. doi:10.7150/ijbs.72386. https://www.ijbs.com/v18p4151.htm
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Abstract

Graphic abstract

Lung adenocarcinoma (LUAD) causes severe cancer death worldwide. E2F2 is a canonical transcription factor implicated in transcription regulation, cell cycle and tumorigenesis. The role of E2F2 as well as its transcription regulatory network in LUAD remains obscure. In this study, we constructed a weighted gene co-expression network and identified several key modules and networks overrepresented in LUAD, including the E2F2-centered transcription regulatory network. Function analysis revealed that E2F2 overexpression accelerated cell growth, cell cycle progression and cell motility in LUAD cells whereas E2F2 knockdown inhibited these malignant phenotypes. Mechanistic investigations uncovered various E2F2-regulated downstream genes and oncogenic signaling pathways. Notably, three core transcription factors of E2F2, B-Myb and FOXM1 from the LUAD transcription regulatory network exhibited positive expression correlation, associated with each other, mutually transactivated each other, and regulated similar downstream gene cascades, hence constituting a consolidated core transcription regulatory circuitry. Moreover, E2F2 could promote and was essentially required for LUAD growth in orthotopic mouse models. Prognosis modeling revealed that a two-gene signature of E2F2 and PLK1 from the transcription regulatory circuitry remarkably stratified patients into low- and high-risk groups. Collectively, our results clarified the critical roles of E2F2 and the exquisite core transcription regulatory circuitry of E2F2/B-Myb/FOXM1 in LUAD progression.

Keywords: Lung adenocarcinoma, E2F2, Transcriptional regulation, B-Myb, FOXM1


Citation styles

APA
Du, K., Sun, S., Jiang, T., Liu, T., Zuo, X., Xia, X., Liu, X., Wang, Y., Bu, Y. (2022). E2F2 promotes lung adenocarcinoma progression through B-Myb- and FOXM1-facilitated core transcription regulatory circuitry. International Journal of Biological Sciences, 18(10), 4151-4170. https://doi.org/10.7150/ijbs.72386.

ACS
Du, K.; Sun, S.; Jiang, T.; Liu, T.; Zuo, X.; Xia, X.; Liu, X.; Wang, Y.; Bu, Y. E2F2 promotes lung adenocarcinoma progression through B-Myb- and FOXM1-facilitated core transcription regulatory circuitry. Int. J. Biol. Sci. 2022, 18 (10), 4151-4170. DOI: 10.7150/ijbs.72386.

NLM
Du K, Sun S, Jiang T, Liu T, Zuo X, Xia X, Liu X, Wang Y, Bu Y. E2F2 promotes lung adenocarcinoma progression through B-Myb- and FOXM1-facilitated core transcription regulatory circuitry. Int J Biol Sci 2022; 18(10):4151-4170. doi:10.7150/ijbs.72386. https://www.ijbs.com/v18p4151.htm

CSE
Du K, Sun S, Jiang T, Liu T, Zuo X, Xia X, Liu X, Wang Y, Bu Y. 2022. E2F2 promotes lung adenocarcinoma progression through B-Myb- and FOXM1-facilitated core transcription regulatory circuitry. Int J Biol Sci. 18(10):4151-4170.

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