CHAF1B promotes proliferation and reduces apoptosis in 95‑D lung cancer cells and predicts a poor prognosis in non‑small cell lung cancer

Duan,Yan; Liu,Tanzhen; Li,Shengwen; Huang,Mingguang; Li,Xiaoyu; Zhao,Hui; Li,Jianqiang

doi:10.3892/or.2019.6994

CHAF1B promotes proliferation and reduces apoptosis in 95‑D lung cancer cells and predicts a poor prognosis in non‑small cell lung cancer

Authors:
- Yan Duan
- Tanzhen Liu
- Shengwen Li
- Mingguang Huang
- Xiaoyu Li
- Hui Zhao
- Jianqiang Li
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Affiliations: Department of Internal Medicine, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China, Department of Respiratory and Critical Medicine, The Second Affiliated Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China, Department of Respiratory and Critical Medicine, Shanxi Provincial People's Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi 030012, P.R. China, Intensive Care Unit, Shanxi Provincial Cancer Hospital, The Affiliated Tumor Hospital of Shanxi Medical University, Taiyuan, Shanxi 030013, P.R. China
Published online on: February 1, 2019 https://doi.org/10.3892/or.2019.6994
Pages: 2518-2528

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Abstract

Chromatin assembly factor 1 subunit B (CHAF1B) participates in DNA synthesis and repair. High CHAF1B expression has been associated with a poor prognosis in several types of cancers. However, no study has evaluated the clinical significance and biological function of CHAF1B in non‑small cell lung cancer (NSCLC). In the present study, we aimed to investigate CHAF1B expression and its role in NSCLC. In the present study, it was revealed that CHAF1B was highly expressed in NSCLC lung tissues and 95‑D cells. Kaplan‑Meier survival analysis indicated that high CHAF1B expression in tumour tissue was associated with poor clinical outcomes in NSCLC patients. Multivariate Cox analyses revealed that lymph node metastasis, tumour‑node‑metastasis (TNM) stage and CHAF1B expression were independent prognostic factors in NSCLC patients. Moreover, CHAF1B knockdown in 95‑D cells markedly inhibited tumour proliferation, reduced colony formation, induced cell cycle arrest and promoted apoptosis. In vivo studies demonstrated that CHAF1B knockdown inhibited the growth of transplanted tumours. Furthermore, our results revealed that the mechanism by which CHAF1B induced apoptosis was mediated by the activation of the p53‑dependent apoptotic signalling pathway (BAK/Bcl‑2/caspase‑3) in 95‑D cells. These data indicated that CHAF1B plays an important role in tumourigenesis and may be a therapeutic molecular target to counter NSCLC progression.

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1	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2017. CA Cancer J Clin. 67:7–30. 2017. View Article : Google Scholar : PubMed/NCBI
2	Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ and He J: Cancer statistics in China, 2015. CA Cancer J Clin. 66:115–132. 2016. View Article : Google Scholar : PubMed/NCBI
3	Chan BA and Hughes BG: Targeted therapy for non-small cell lung cancer: Current standards and the promise of the future. Transl Lung Cancer Res. 4:36–54. 2015.PubMed/NCBI
4	Chen Z, Fillmore CM, Hammerman PS, Kim CF and Wong K-K: Non-small-cell lung cancers: A heterogeneous set of diseases. Nature Rev Cancer. 14:5352014. View Article : Google Scholar
5	Smith S and Stillman B: Purification and characterization of CAF-I, a human cell factor required for chromatin assembly during DNA replication in vitro. Cell. 58:15–25. 1989. View Article : Google Scholar : PubMed/NCBI
6	Verreault A, Kaufman PD, Kobayashi R and Stillman B: Nucleosome assembly by a complex of CAF-1 and acetylated histones H3/H4. Cell. 87:95–104. 1996. View Article : Google Scholar : PubMed/NCBI
7	Kaufman PD, Kobayashi R, Kessler N and Stillman B: The p150 and p60 subunits of chromatin assembly factor I: A molecular link between newly synthesized histones and DNA replication. Cell. 81:1105–1114. 1995. View Article : Google Scholar : PubMed/NCBI
8	Evan GI and Vousden KH: Proliferation, cell cycle and apoptosis in cancer. Nature. 411:342–348. 2001. View Article : Google Scholar : PubMed/NCBI
9	Tayrac MD, Saikali S, Aubry M, Bellaud P, Boniface R, Quillien V and Mosser J: Prognostic significance of EDN/RB, HJURP, p60/CAF-1 and PDLI4, four new markers in high-grade gliomas. PLoS One. 8:e733322013. View Article : Google Scholar : PubMed/NCBI
10	Tayrac MD, Aubry M, Saïkali S, Etcheverry A, Surbled C, Guénot F, Galibert MD, Hamlat A, Lesimple T, Quillien V, et al: A 4-Gene signature associated with clinical outcome in high-grade gliomas. Clin Cancer Res. 17:317–327. 2011. View Article : Google Scholar : PubMed/NCBI
11	Staibano S, Mascolo M, Mancini FP, Kisslinger A, Salvatore G, Di Benedetto M, Chieffi P, Altieri V, Prezioso D, Ilardi G, et al: Overexpression of chromatin assembly factor-1 (CAF-1) p60 is predictive of adverse behaviour of prostatic cancer. Histopathology. 54:580–589. 2009. View Article : Google Scholar : PubMed/NCBI
12	Staibano S, Mignogna C, Lo Muzio L, Mascolo M, Salvatore G, Di Benedetto M, Califano L, Rubini C and De Rosa G: Chromatin assembly factor-1 (CAF-1)-mediated regulation of cell proliferation and DNA repair: A link with the biological behaviour of squamous cell carcinoma of the tongue? Histopathology. 50:911–919. 2007. View Article : Google Scholar : PubMed/NCBI
13	Polo SE, Theocharis SE, Klijanienko J, Savignoni A, Asselain B, Vielh P and Almouzni G: Chromatin assembly factor-1, a marker of clinical value to distinguish quiescent from proliferating cells. Cancer Res. 64:2371–2381. 2004. View Article : Google Scholar : PubMed/NCBI
14	Staibano S, Mascolo M, Rocco A, Lo Muzio L, Ilardi G, Siano M, Pannone G, Vecchione ML, Nugnes L, Califano L, et al: The proliferation marker chromatin assembly factor-1 is of clinical value in predicting the biological behaviour of salivary gland tumours. Oncol Rep. 25:13–22. 2011.PubMed/NCBI
15	Polo SE, Theocharis SE, Grandin L, Gambotti L, Antoni G, Savignoni A, Asselain B, Patsouris E and Almouzni G: Clinical significance and prognostic value of chromatin assembly factor-1 overexpression in human solid tumours. Histopathology. 57:716–724. 2010. View Article : Google Scholar : PubMed/NCBI
16	Mascolo M, Vecchione ML, Ilardi G, Scalvenzi M, Molea G, Di Benedetto M, Nugnes L, Siano M, De Rosa G and Staibano S: Overexpression of chromatin assembly Factor-1/p60 helps to predict the prognosis of melanoma patients. BMC Cancer. 10:632010. View Article : Google Scholar : PubMed/NCBI
17	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2^−ΔΔCT method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
18	Naito S, von Eschenbach AC, Giavazzi R and Fidler IJ: Growth and metastasis of tumour cells isolated from a human renal cell carcinoma implanted into different organs of nude mice. Cancer Res. 46:4109–4115. 1986.PubMed/NCBI
19	Hall PA and Levison DA: Review: Assessment of cell proliferation in histological material. J Clin Pathol. 43:184–192. 1990. View Article : Google Scholar : PubMed/NCBI
20	Nabatiyan A and Krude T: Silencing of chromatin assembly factor 1 in human cells leads to cell death and loss of chromatin assembly during DNA synthesis. Mol Cell Biol. 24:2853–2862. 2004. View Article : Google Scholar : PubMed/NCBI
21	Gerdes J, Schwab U, Lemke H and Stein H: Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation. Int J Cancer. 31:13–20. 1983. View Article : Google Scholar : PubMed/NCBI
22	Brown DC and Gatter KC: Monoclonal antibody Ki-67: Its use in histopathology. Histopathology. 17:489–503. 1990. View Article : Google Scholar : PubMed/NCBI
23	Mascolo M, Ilardi G, Merolla F, Russo D, Vecchione ML, de Rosa G and Staibano S: Tissue microarray-Based evaluation of chromatin assembly factor-1 (CAF-1)/p60 as tumour prognostic marker. Int J Mol Sci. 13:11044–11062. 2012. View Article : Google Scholar : PubMed/NCBI
24	Schaal C and Chellappan SP: Nicotine-mediated cell proliferation and tumor progression in smoking-related cancers. Mol Cancer Res. 12:14–23. 2014. View Article : Google Scholar : PubMed/NCBI
25	Barbieri E, De Preter K, Capasso M, Chen Z, Hsu DM, Tonini GP, Lefever S, Hicks J, Versteeg R, Pession A, et al: Histone chaperone CHAF1A inhibits differentiation and promotes aggressive neuroblastoma. Cancer Res. 74:765–774. 2014. View Article : Google Scholar : PubMed/NCBI
26	Levine AJ, Feng Z, Mak TW, You H and Jin S: Coordination and communication between the p53 and IGF-1-AKT-TOR signal transduction pathways. Genes Dev. 20:267–275. 2006. View Article : Google Scholar : PubMed/NCBI
27	Marchenko ND, Zaika A and Moll UM: Death signal-induced localization of p53 protein to mitochondria. A potential role in apoptotic signaling. J Biol Chem. 275:16202–16212. 2000. View Article : Google Scholar : PubMed/NCBI
28	Kuwana T, Mackey MR, Perkins G, Ellisman MH, Latterich M, Schneiter R, Green DR and Newmeyer DD: Bid, bax, and lipids cooperate to form supramolecular openings in the outer mitochondrial membrane. Cell. 111:331–342. 2002. View Article : Google Scholar : PubMed/NCBI
29	Cory S and Adams JM: The Bcl2 family: Regulators of the cellular life-or-death switch. Nat Rev Cancer. 2:647–656. 2002. View Article : Google Scholar : PubMed/NCBI
30	Leu J, Dumont P, Hafey M, Murphy ME and George DL: Mitochondrial p53 activates Bak and causes disruption of a Bak-Mcll complex. Nat Cell Biol. 6:443–450. 2004. View Article : Google Scholar : PubMed/NCBI
31	Tomita Y, Marchenko N, Erster S, Nemajerova A, Dehner A, Klein C, Pan H, Kessler H, Pancoska P and Moll UM: WT p53, but not tumor-derived mutants, bind to Bcl2 via the DNA binding domain and induce mitochondrial permeabilization. J Biol Chem. 281:8600–8606. 2006. View Article : Google Scholar : PubMed/NCBI
32	Giono LE and Manfredi JJ: The p53 tumor suppressor participates in multiple cell cycle checkpoints. J Cell Physiol. 209:13–20. 2006. View Article : Google Scholar : PubMed/NCBI
33	Nurse P: Universal control mechanism regulating onset of M-phase. Nature. 344:503–508. 1990. View Article : Google Scholar : PubMed/NCBI