ANP32E contributes to gastric cancer progression via NUF2 upregulation

Zhu,Xiaowen; Zou,Yumin; Wu,Tong; Ni,Jian; Tan,Qingyun; Wang,Qingdong; Zhang,Meijia

doi:10.3892/mmr.2022.12791

ANP32E contributes to gastric cancer progression via NUF2 upregulation

Authors:
- Xiaowen Zhu
- Yumin Zou
- Tong Wu
- Jian Ni
- Qingyun Tan
- Qingdong Wang
- Meijia Zhang
View Affiliations

Affiliations: Department of Proctology, The First Affiliated Hospital of Jiamusi University, Jiamusi, Heilongjiang 154003, P.R. China, Department of Central Sterile Supply, The First Affiliated Hospital of Jiamusi University, Jiamusi, Heilongjiang 154003, P.R. China, Department of Anesthesiology, The First Affiliated Hospital of Jiamusi University, Jiamusi, Heilongjiang 154003, P.R. China, Department of Otolaryngology, The First Affiliated Hospital of Jiamusi University, Jiamusi, Heilongjiang 154003, P.R. China
Published online on: July 6, 2022 https://doi.org/10.3892/mmr.2022.12791
Article Number: 275
Copyright: © Zhu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Acidic nuclear phosphoprotein 32 family member E (ANP32E) is a histone chaperone that removes H2A.Z from chromatin. ANP32E is implicated in numerous cellular processes, including cell proliferation, apoptosis and cell differentiation. Increasing evidence suggests that dysregulation of ANP32E expression is strongly associated with carcinogenesis. However, the relationship between ANP32E in the development of gastric cancer (GC) is unknown. The present study aimed to explore the potential role of ANP32E in the development of GC using gain‑of‑function, loss‑of‑function, CCK‑8, colony formation, apoptosis, reverse transcription‑quantitative PCR, immunoblotting and luciferase reporter assay. The results of the present study demonstrated that ANP32E expression levels were significantly increased in GC tissues. ANP32E knockdown markedly inhibited GC cell proliferation and colony formation and significantly induced GC cell apoptosis, whereas overexpression of ANP32E significantly induced GC cell malignancy. Furthermore, the results demonstrated that there was a positive association between ANP32E and NUF2 component of NDC80 kinetochore complex (NUF2) expression levels. By assessing NUF2 expression levels, it was demonstrated that ANP32E promoted tumor cell proliferation and inhibited cell apoptosis by increasing NUF2 expression levels in GC cell lines. In conclusion, the present study indicated that ANP32E may function as an efficient oncogene, which promotes tumorigenesis of GC cells by inducing NUF2 expression.

View Figures

View References

1	Smyth EC, Nilsson M, Grabsch HI, van Grieken NC and Lordick F: Gastric cancer. Lancet. 396:635–648. 2020. View Article : Google Scholar : PubMed/NCBI
2	Qin Y, Tong X, Fan J, Liu Z, Zhao R, Zhang T, Suo C, Chen X and Zhao G: Global burden and trends in incidence, mortality, and disability of stomach cancer from 1990 to 2017. Clin Transl Gastroenterol. 12:e004062021. View Article : Google Scholar : PubMed/NCBI
3	Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A and Bray F: Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 71:209–249. 2021. View Article : Google Scholar : PubMed/NCBI
4	Cancer Genome Atlas Research Network, . Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 513:202–209. 2014. View Article : Google Scholar : PubMed/NCBI
5	Cristescu R, Lee J, Nebozhyn M, Kim KM, Ting JC, Wong SS, Liu J, Yue YG, Wang J, Yu K, et al: Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes. Nat Med. 21:449–456. 2015. View Article : Google Scholar : PubMed/NCBI
6	Mao Z, Pan L, Wang W, Sun J, Shan S, Dong Q, Liang X, Dai L, Ding X, Chen S, et al: Anp32e, a higher eukaryotic histone chaperone directs preferential recognition for H2A.Z. Cell Res. 24:389–399. 2014. View Article : Google Scholar : PubMed/NCBI
7	Lorén V, Garcia-Jaraquemada A, Naves JE, Carmona X, Mañosa M, Aransay AM, Lavin JL, Sánchez I, Cabré E, Manyé J and Domènech E: ANP32E, a protein involved in steroid-refractoriness in ulcerative colitis, identified by a systems biology approach. J Crohns Colitis. 13:351–361. 2019. View Article : Google Scholar : PubMed/NCBI
8	Xiong Z, Ye L, Zhenyu H, Li F, Xiong Y, Lin C, Wu X, Deng G, Shi W, Song L, et al: ANP32E induces tumorigenesis of triple-negative breast cancer cells by upregulating E2F1. Mol Oncol. 12:896–912. 2018. View Article : Google Scholar : PubMed/NCBI
9	Gursoy-Yuzugullu O, Ayrapetov MK and Price BD: Histone chaperone Anp32e removes H2A.Z from DNA double-strand breaks and promotes nucleosome reorganization and DNA repair. Proc Natl Acad Sci USA. 112:7507–7512. 2015. View Article : Google Scholar : PubMed/NCBI
10	Alatwi HE and Downs JA: Removal of H2A.Z by INO80 promotes homologous recombination. EMBO Rep. 16:986–994. 2015. View Article : Google Scholar : PubMed/NCBI
11	Murphy KE, Meng FW, Makowski CE and Murphy PJ: Genome-wide chromatin accessibility is restricted by ANP32E. Nat Commun. 11:50632020. View Article : Google Scholar : PubMed/NCBI
12	Mikami Y, Hori T, Kimura H and Fukagawa T: The functional region of CENP-H interacts with the Nuf2 complex that localizes to centromere during mitosis. Mol Cell Biol. 25:1958–1970. 2005. View Article : Google Scholar : PubMed/NCBI
13	Wang Y, Tan PY, Handoko YA, Sekar K, Shi M, Xie C, Jiang XD, Dong QZ, Goh BKP, Ooi LL, et al: NUF2 is a valuable prognostic biomarker to predict early recurrence of hepatocellular carcinoma after surgical resection. Int J Cancer. 145:662–670. 2019. View Article : Google Scholar : PubMed/NCBI
14	Liu Q, Dai SJ, Li H, Dong L and Peng YP: Silencing of NUF2 inhibits tumor growth and induces apoptosis in human hepatocellular carcinomas. Asian Pac J Cancer Prev. 15:8623–8629. 2014. View Article : Google Scholar : PubMed/NCBI
15	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
16	Song Z, Wu Y, Yang J, Yang D and Fang X: Progress in the treatment of advanced gastric cancer. Tumour Biol. 39:10104283177146262017. View Article : Google Scholar : PubMed/NCBI
17	Pellino A, Riello E, Nappo F, Brignola S, Murgioni S, Djaballah SA, Lonardi S, Zagonel V, Rugge M, Loupakis F and Fassan M: Targeted therapies in metastatic gastric cancer: Current knowledge and future perspectives. World J Gastroenterol. 25:5773–5788. 2019. View Article : Google Scholar : PubMed/NCBI
18	Huang J, Gao W, Liu H, Yin G, Duan H, Huang Z and Zhang Y: Up-regulated ANP32E promotes the thyroid carcinoma cell proliferation and migration via activating AKT/mTOR/HK2-mediated glycolysis. Gene. 750:1446812020. View Article : Google Scholar : PubMed/NCBI
19	Wang L, Li J, Li Y and Pang LB: Hsa-let-7c exerts an anti-tumor function by negatively regulating ANP32E in lung adenocarcinoma. Tissue Cell. 65:1013722020. View Article : Google Scholar : PubMed/NCBI
20	Zhang J, Lan Z, Qiu G, Ren H, Zhao Y, Gu Z, Li Z, Feng L, He J and Wang C: Over-expression of ANP32E is associated with poor prognosis of pancreatic cancer and promotes cell proliferation and migration through regulating β-catenin. BMC Cancer. 20:10652020. View Article : Google Scholar : PubMed/NCBI
21	Chen L, Gao Y, Zhu L, Song H, Zhao L, Liu A, Zhang G and Shi G: Establishment and characterization of a GES-1 human gastric epithelial cell line stably expressing miR-23a. Oncol Lett. 16:977–983. 2018.PubMed/NCBI
22	Keates S, Sougioultzis S, Keates AC, Zhao D, Peek RM Jr, Shaw LM and Kelly CP: cag+ Helicobacter pylori induce transactivation of the epidermal growth factor receptor in AGS gastric epithelial cells. J Biol Chem. 276:48127–48134. 2001. View Article : Google Scholar : PubMed/NCBI
23	Akagi T and Kimoto T: Human cell line (HGC-27) derived from the metastatic lymph node of gastric cancer. Acta Med Okayama. 30:215–219. 1976.PubMed/NCBI
24	Motoyama T, Hojo H and Watanabe H: Comparison of seven cell lines derived from human gastric carcinomas. Acta Pathol Jpn. 36:65–83. 1986.PubMed/NCBI
25	Xie X, Jiang S and Li X: Nuf2 is a prognostic-related biomarker and correlated with immune infiltrates in hepatocellular carcinoma. Front Oncol. 11:6213732021. View Article : Google Scholar : PubMed/NCBI
26	Zhai X, Yang Z, Liu X, Dong Z and Zhou D: Identification of NUF2 and FAM83D as potential biomarkers in triple-negative breast cancer. PeerJ. 8:e99752020. View Article : Google Scholar : PubMed/NCBI
27	Fu HL and Shao L: Silencing of NUF2 inhibits proliferation of human osteosarcoma Saos-2 cells. Eur Rev Med Pharmacol Sci. 20:1071–1079. 2016.PubMed/NCBI