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

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.

The Potential Association between E2F2, MDM2 and p16 Protein Concentration and Selected Sociodemographic and Clinicopathological Characteristics of Patients with Oral Squamous Cell Carcinoma

“…E2F2, MDM2 and p16 are some of the key proteins associated with the control of the cell cycle [ 13 , 16 , 27 ]. However, the exact role of E2F2, MDM2 and p16 in prognosis and biological function has not been well established in OSCC.…”

“…In addition, it is involved in apoptosis, inflammation, migration and cell invasion. Some studies have shown that E2F2 can presumably promote tumour development and progression in various types of cancer, including lung adenocarcinoma, breast cancer, ovarian cancer and colorectal cancer [ 12 , 13 ]. MDM2 is an oncoprotein with the ability to negatively regulate and maintain stability of the p53 tumour suppressor protein signalling pathway [ 9 ].…”

A new hope for targeted therapy of ischemia-reperfusion injury: E2F2, an important transcription factor in H/R process

“…E2F2 is a complex molecule, the expression of E2F2 can regulate and accelerate cell growth, cell cycle progression and cell movement, promote the proliferation of hepatocytes and cardiomyocytes, but also inhibit the proliferation of peripheral blood T cells [26,29] . During the process of IRI, whether E2F2 upregulation can be used to accelerate cell proliferation and tissue function recovery in a short term to ght against IRI is worth thinking about.…”

Circ_0000877 accelerates proliferation and immune escape of non‐small cell lung cancer cells by regulating microRNA‐637/E2F2 axis

“…Report from Teng et al verified that miR‐637 suppression was linked to TNM stage and poor prognosis of NSCLC patients and served as a tumor suppressor in NSCLC 17 . E2F2 is a normative transcription factor, which joins in transcription regulation, cell cycle, and tumorigenesis 18 . Several researches uncovered that miRNAs modulated NSCLC cell proliferation and invasion via targeting E2F2 19,20 .…”

“…17 E2F2 is a normative transcription factor, which joins in transcription regulation, cell cycle, and tumorigenesis. 18 Several researches uncovered that miRNAs modulated NSCLC cell proliferation and invasion via targeting E2F2. 19,20 But, whether miR-637 joins in regulating the function of circ_0000877 through targeting E2F2 in NSCLC cells remains unexplored.…”