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Current Pharmaceutical Biotechnology

Editor-in-Chief

ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

Research Article

CCNE1 Promotes Progression and is Associated with Poor Prognosis in Lung Adenocarcinoma

Author(s): Guoliang Ma, Lulu Yang, Jing Dong and Lili Zhang*

Volume 23, Issue 9, 2022

Published on: 14 January, 2022

Page: [1168 - 1178] Pages: 11

DOI: 10.2174/1389201022666211118112935

Price: $65

Abstract

Background: Mounting evidence has shown that Cyclin E1 (CCNE1) facilitates various carcinoma progression, but its function in lung adenocarcinoma (LUAD) remains unclear.

Objective: Our study aims to explore the significance of CCNE1 in clinical progression and study its biological functions in LUAD.

Methods: CCNE1 expressions in LUAD specimens and cells were detected through quantitative realtime polymerase chain reaction (qRT-RCR) and western blot. An immunohistochemistry technique was used to detect CCNE1 expression to explore its association with clinical parameters. The LUAD cells with stable knockdown of CCNE1 were constructed by small interfering RNA. The effect of CCNE1 on LUAD cells proliferation and apoptosis was evaluated through Cell Counting Kit-8 (CCK-8), colony formation, and Annexin V/propidium iodide (AV-PI) assays, respectively. The cell migration and invasion were evaluated by Wound-healing and Transwell assays, respectively. The xenograft and lung metastasis mouse models were introduced to analyze how CCNE1 knockdown affects tumor growth and tumor metastasis.

Results: CCNE1 expression was upregulated in LUAD tissue and cells. CCNE1 knockdown inhibited LUAD cellular malignant behavior in vitro and reduced tumor growth and metastasis in vivo. High expression of CCNE1 was correlated with big tumor size, cancer stage, lymph node metastasis, and poor prognosis.

Conclusion: CCNE1 overexpression promotes LUAD growth, metastasis, and forebode poor prognosis: it can serve as a new prognostic marker of LUAD.

Keywords: CCNE1, lung adenocarcinoma, progression, prognosis, metastasis, in vitro.

Graphical Abstract

[1]
Siegel, R.L.; Miller, K.D.; Jemal, A.; Fedewa, S.A.; Butterly, L.F.; Anderson, J.C.; Cercek, A.; Smith, R.A.; Jemal, A. Cancer statistics, 2020. Ca Cancer J. Clin., 2020, 70(1), 7-30. [http://dx.doi.org/10.3322/caac.21590]. [PMID: 31912902].
[2]
Zheng, M. Classification and pathology of lung cancer. Surg. Oncol. Clin. Am., 2016, 25(3), 447-468. [http://dx.doi.org/10.1016/j.soc.2016.02.003]. [PMID: 27261908].
[3]
Calvayrac, O.; Pradines, A.; Pons, E.; Mazières, J.; Guibert, N. Molecular biomarkers for lung adenocarcinoma. Eur. Respir. J., 2017, 49(4)1601734 [http://dx.doi.org/10.1183/13993003.01734-2016]. [PMID: 28381431].
[4]
Xue, C.; Hu, Z.; Jiang, W.; Zhao, Y.; Xu, F.; Huang, Y.; Zhao, H.; Wu, J.; Zhang, Y.; Zhao, L.; Zhang, J.; Chen, L.; Zhang, L. National survey of the medical treatment status for non-small cell lung cancer (NSCLC) in China. Lung Cancer, 2012, 77(2), 371-375. [http://dx.doi.org/10.1016/j.lungcan.2012.04.014]. [PMID: 22579298].
[5]
Huang, P.; Cao, K.; Zhao, H. Screening of critical genes in lung adenocarcinoma via network analysis of gene expression profile. Pathol. Oncol. Res., 2014, 20(4), 853-858. [http://dx.doi.org/10.1007/s12253-014-9764-z]. [PMID: 24859971].
[6]
Möröy, T.; Geisen, C.; Cyclin, E.; Cyclin, E. Int. J. Biochem. Cell Biol., 2004, 36(8), 1424-1439. [http://dx.doi.org/10.1016/j.biocel.2003.12.005]. [PMID: 15147722].
[7]
Nakayama, N.; Nakayama, K.; Shamima, Y.; Ishikawa, M.; Katagiri, A.; Iida, K.; Miyazaki, K. Gene amplification CCNE1 is related to poor survival and potential therapeutic target in ovarian cancer. Cancer, 2010, 116(11), 2621-2634.
[8]
Shariat, S.F.; Ashfaq, R.; Sagalowsky, A.I.; Lotan, Y. Correlation of cyclin D1 and E1 expression with bladder cancer presence, invasion, progression, and metastasis. Hum. Pathol., 2006, 37(12), 1568-1576. [http://dx.doi.org/10.1016/j.humpath.2006.05.017]. [PMID: 16949911].
[9]
Kim, B.; Shin, H.C.; Heo, Y.J.; Ha, S.Y.; Jang, K.T.; Kim, S.T.; Kang, W.K.; Lee, J.; Kim, K.M. CCNE1 amplification is associated with liver metastasis in gastric carcinoma. Pathol. Res. Pract., 2019, 215(8)152434 [http://dx.doi.org/10.1016/j.prp.2019.152434]. [PMID: 31178228].
[10]
Zhao, Z.M.; Yost, S.E.; Hutchinson, K.E.; Li, S.M.; Yuan, Y.C.; Noorbakhsh, J.; Liu, Z.; Warden, C.; Johnson, R.M.; Wu, X.; Chuang, J.H.; Yuan, Y. CCNE1 amplification is associated with poor prognosis in patients with triple negative breast cancer. BMC Cancer, 2019, 19(1), 96. [http://dx.doi.org/10.1186/s12885-019-5290-4]. [PMID: 30665374].
[11]
Zhao, H.; Wang, J.; Zhang, Y.; Yuan, M.; Yang, S.; Li, L.; Yang, H. Prognostic values of ccne1 amplification and overexpression in cancer patients: A systematic review and meta-analysis. J. Cancer, 2018, 9(13), 2397-2407. [http://dx.doi.org/10.7150/jca.24179]. [PMID: 30026836].
[12]
Han, Z.; Zhang, Y.; Yang, Q.; Liu, B.; Wu, J.; Zhang, Y.; Yang, C.; Jiang, Y. Mir-497 and mir-34a retard lung cancer growth by co-inhibiting cyclin E1 (ccne1). Oncotarget, 2015, 6(15), 13149-13163. [http://dx.doi.org/10.18632/oncotarget.3693]. [PMID: 25909221].
[13]
Koutsami, M.K.; Tsantoulis, P.K.; Kouloukoussa, M.; Apostolopoulou, K.; Pateras, I.S.; Spartinou, Z.; Drougou, A.; Evangelou, K.; Kittas, C.; Bartkova, J.; Bartek, J.; Gorgoulis, V.G. Centrosome abnormalities are frequently observed in non-small-cell lung cancer and are associated with aneuploidy and cyclin E overexpression. J. Pathol., 2006, 209(4), 512-521. [http://dx.doi.org/10.1002/path.2005]. [PMID: 16739112].
[14]
Tsuta, K.; Kawago, M.; Yoshida, A.; Sekine, S.; Asamura, H.; Furuta, K.; Kushima, R. Primary lung adenocarcinoma with morule-like components: a unique histologic hallmark of aggressive behavior and egfr mutation. Lung Cancer, 2014, 85(1), 12-18. [http://dx.doi.org/10.1016/j.lungcan.2014.03.022]. [PMID: 24768118].
[15]
de Maturana, E.L.; Rava, M.; Anumudu, C.; Sáez, O.; Alonso, D.; Malats, N. Bladder cancer genetic susceptibility. a systematic review. Bladder Cancer, 2018, 4(2), 215-226. [http://dx.doi.org/10.3233/BLC-170159]. [PMID: 29732392].
[16]
Aziz, K.; Limzerwala, J.F.; Sturmlechner, I.; Hurley, E.; Zhang, C.; Jeganathan, K.B.; Nelson, G.; Bronk, S.; Fierro Velasco, R.O.; van Deursen, E.J.; O’Brien, D.R.; Kocher, J.A.; Youssef, S.A.; van Ree, J.H.; de Bruin, A.; van den Bos, H.; Spierings, D.C.J.; Foijer, F.; van de Sluis, B.; Roberts, L.R.; Gores, G.J.; Li, H.; van Deursen, J.M. Ccne1 overexpression causes chromosome instability in liver cells and liver tumor development in mice. Gastroenterology, 2019, 157(1), 210-226. [http://dx.doi.org/10.1053/j.gastro.2019.03.016]. [PMID: 30878468].
[17]
Zhang, C.; Zhu, Q.; Gu, J.; Chen, S.; Li, Q.; Ying, L. Down-regulation of ccne1 expression suppresses cell proliferation and sensitizes gastric carcinoma cells to cisplatin. Biosci. Rep., 2019, 39(6)BSR20190381 [http://dx.doi.org/10.1042/BSR20190381]. [PMID: 31072916].
[18]
Gurzov, E.N.; Izquierdo, M. Cyclin E1 knockdown induces apoptosis in cancer cells. Neurol. Res., 2006, 28(5), 493-499. [http://dx.doi.org/10.1179/016164106X115143]. [PMID: 16808878].

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