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

作者全名："Du, Kailong; Sun, Shijie; Jiang, Tinghui; Liu, Tao; Zuo, Xiaofeng; Xia, Xing; Liu, Xianjun; Wang, Yitao; Bu, Youquan"

作者地址："[Du, Kailong; Sun, Shijie; Jiang, Tinghui; Liu, Tao; Zuo, Xiaofeng; Xia, Xing; Liu, Xianjun; Wang, Yitao; Bu, Youquan] Chongqing Med Univ, Coll Basic Med Sci, Dept Biochem & Mol Biol, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China; [Du, Kailong; Sun, Shijie; Jiang, Tinghui; Liu, Tao; Zuo, Xiaofeng; Xia, Xing; Liu, Xianjun; Wang, Yitao; Bu, Youquan] Chongqing Med Univ, Mol Med & Canc Res Ctr, Chongqing 400016, Peoples R China"

通信作者："Wang, YT; Bu, YQ (通讯作者)，Chongqing Med Univ, Coll Basic Med Sci, Dept Biochem & Mol Biol, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China."

来源：INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:000821460600001

JCR分区：Q1

影响因子：9.2

年份：2022

卷号：18

期号：10

开始页：4151

结束页：4170

文献类型：Article

关键词：Lung adenocarcinoma; Transcriptional regulation; B-Myb; FOXM1

摘要："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."

基金机构："National Natural Science Foundation of China [81672301, 81902824]; Chongqing Municipal Science and Technology Commission [cstc2021jcyj-msxmX0186]"

基金资助正文："This work was supported in part by grants from the National Natural Science Foundation of China (No. 81672301 to YB and No. 81902824 to YW), the Chongqing Municipal Science and Technology Commission (No. cstc2021jcyj-msxmX0186)."