Research Paper Volume 13, Issue 2 pp 2604—2625
Knockdown of CENPF inhibits the progression of lung adenocarcinoma mediated by ERβ2/5 pathway
- 1 Department of Thoracic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China
- 2 Department of Geriatrics, Zhongnan Hospital of Wuhan University, Wuhan, China
- 3 Division of Thoracic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
Received: May 9, 2020 Accepted: September 5, 2020 Published: January 10, 2021
https://doi.org/10.18632/aging.202303How to Cite
Copyright: © 2021 Hexiao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Many studies have reported that estrogen (E2) promotes lung cancer by binding to nuclear estrogen receptors (ER), and altering ER related nuclear protein expressions. With the GEO database analysis, Human centromere protein F (CENPF) is highly expressed in lung adenocarcinoma (LUAD), and the co-expression of CENPF and ERβ was found in the nucleus of LUAD cells through immunofluorescence. We identified the nuclear protein CENPF and explored its relationship with the ER pathway. CENPF and ERβ2/5 were related with T stage and poor prognosis (P<0.05). CENPF knockout significantly inhibited LUAD cell growth, the tumor growth of mice and the expression of ERβ2/5 (P<0.05). The protein expression of CENPF and ERβ2/5 in the CENPF-Knockdown+Fulvestrant group was lower than CENPF- Negative Control +Fulvestrant group (P=0.002, 0.004, 0.001) in A549 cells. The tumor size and weight of the CENPF-Knockdown+Fulvestrant group were significantly lower than CENPF- Negative Control +Fulvestrant group (P=0.001, 0.039) in nude mice. All the results indicated that both CENPF and ERβ2/5 play important roles in the progression of LUAD, and knockdown CENPF can inhibit the progression of LUAD by inhibiting the expression of ER2/5. Thus, the development of inhibitors against ERβ2/5 and CENPF remained more effective in improving the therapeutic effect of LUAD.
Abbreviations
ER: Estrogen receptors; AP-1: Activator protein 1; SP-1: Specificity protein 1; IL-6: Interleukin 6; EGF: Epidermal growth factor; CENPF: centromere protein F; LUAD: lung adenocarcinoma; BPL: benign pulmonary lesions; FBS: fetal bovine serum; FDR: false discovery rate; FC: fold change; WGCNA: weighted gene co-expression network analysis; GEPIA: Gene Expression Profiling Interactive Analysis; TCGA: The Cancer Genome Atlas; KD: knockdown; NC: negative control; ERE: estrogen response element.