Structural Maintenance of Chromosome Protein 4 Promotes the Progression of Cardia Adenocarcinoma via Regulation of the Wnt/β-catenin Signaling Pathway


Цитировать

Полный текст

Аннотация

Background:Structural maintenance of chromosome protein 4 (SMC4) is crucial for chromosome assembly and separation, but its role and mechanism in cardia adenocarcinoma (CA) are unknown.

Methods:SMC4 expression levels were initially detected by protein profiling in 20 pairs of CA tumor tissues and adjacent normal tissues. The level of SMC4 expression in CA cells was then evaluated using a western blot analysis. Cell proliferation was evaluated by CCK-8 and clone formation tests. Scratch and transwell tests were used to investigate cell migration as well as invasion, while through the flow cytometry, we examined the cell apoptosis and progression of the cell cycle. The regulatory effects of the epithelial-mesenchymal transition (EMT) and the Wnt/β- catenin pathway were investigated using western blot. A tumorigenesis experiment was used to investigate the influence of SMC4 on tumor development in nude mice.

Results:This study showed overexpression of SMC4 in CA tissues and cells. Knockdown of SMC4 can significantly inhibit the proliferation, migration and invasion, stimulate cell apoptosis, induce cell cycle arrest in the G0/G1 phase of CA cells, and inhibit tumor growth in vivo. In addition, down-regulation of SMC4 resulted in decreased expression of Bcl-2, Cyclin D1, CDK4, CDK6, β-catenin, phosphorylated GSK-3β, N-cadherin, and Vimentin, with an increased level of proteins, i.e., Bax, cleaved-caspase3, and E-cadherin. When SMC4 was overexpressed, these effects were reversed.

Conclusion:SMC4 can facilitate the biological progression of CA, suggesting that SMC4 could be a potential therapeutic target for the disease.

Об авторах

Mengqi Zhu

Department of Surgical Oncology, The First Affiliated Hospital of Bengbu Medical College

Email: info@benthamscience.net

Xinxin Zhang

Department of Surgical Oncology, The First Affiliated Hospital of Bengbu Medical College

Email: info@benthamscience.net

Kaiji Gao

Department of Surgical Oncology, The First Affiliated Hospital of Bengbu Medical College

Email: info@benthamscience.net

Lingmei Zhang

Department of Gynecological Oncology,, The First Affiliated Hospital of Bengbu Medical College

Email: info@benthamscience.net

Xiaojia Feng

Department of Surgical Oncology, The First Affiliated Hospital of Bengbu Medical College

Email: info@benthamscience.net

Hui Wang

Department of Surgical Oncology, The First Affiliated Hospital of Bengbu Medical College

Email: info@benthamscience.net

Jing Li

Department of Surgical Oncology, The First Affiliated Hospital of Bengbu Medical College

Email: info@benthamscience.net

Jianguang Jia

Department of Surgical Oncology, The First Affiliated Hospital of Bengbu Medical College

Автор, ответственный за переписку.
Email: info@benthamscience.net

Список литературы

  1. Chen, W.; Zheng, R.; Baade, P.D.; Zhang, S.; Zeng, H.; Bray, F.; Jemal, A.; Yu, X.Q.; He, J. Cancer statistics in China, 2015. CA Cancer J. Clin., 2016, 66(2), 115-132. doi: 10.3322/caac.21338 PMID: 26808342
  2. Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2018, 68(6), 394-424. doi: 10.3322/caac.21492 PMID: 30207593
  3. Rawla, P.; Barsouk, A. Epidemiology of gastric cancer: Global trends, risk factors and prevention. Prz. Gastroenterol., 2019, 14(1), 26-38. doi: 10.5114/pg.2018.80001 PMID: 30944675
  4. Olefson, S.; Moss, S.F. Obesity and related risk factors in gastric cardia adenocarcinoma. Gastric Cancer, 2015, 18(1), 23-32. doi: 10.1007/s10120-014-0425-4 PMID: 25209115
  5. Jia, J.; Zhang, X.; Zhan, D.; Li, J.; Li, Z.; Li, H.; Qian, J. LncRNA H19 interacted with miR‐130a‐3p and miR‐17‐5p to modify radio‐resistance and chemo‐sensitivity of cardiac carcinoma cells. Cancer Med., 2019, 8(4), 1604-1618. doi: 10.1002/cam4.1860 PMID: 30843379
  6. Xu, H.; Zhang, L.; Miao, J.; Liu, S.; Liu, H.; Jia, T.; Zhang, Q. Patterns of recurrence in adenocarcinoma of the esophagogastric junction: A retrospective study. World J. Surg. Oncol., 2020, 18(1), 144. doi: 10.1186/s12957-020-01917-5 PMID: 32593312
  7. Cao, J.; Yang, T.; Wang, G.; Zhang, H.; You, Y.; Chen, J.; Yang, J.; Yang, W. Analysis of the clinicopathological features and prognostic factors in 734 cases of Chinese Hui and Han patients with adenocarcinoma of the esophagogastric junction. Surg. Oncol., 2018, 27(3), 556-562. doi: 10.1016/j.suronc.2018.07.008 PMID: 30217319
  8. Ajani, J.A.; D’Amico, T.A.; Bentrem, D.J.; Chao, J.; Corvera, C.; Das, P.; Denlinger, C.S.; Enzinger, P.C.; Fanta, P.; Farjah, F.; Gerdes, H.; Gibson, M.; Glasgow, R.E.; Hayman, J.A.; Hochwald, S.; Hofstetter, W.L.; Ilson, D.H.; Jaroszewski, D.; Johung, K.L.; Keswani, R.N.; Kleinberg, L.R.; Leong, S.; Ly, Q.P.; Matkowskyj, K.A.; McNamara, M.; Mulcahy, M.F.; Paluri, R.K.; Park, H.; Perry, K.A.; Pimiento, J.; Poultsides, G.A.; Roses, R.; Strong, V.E.; Wiesner, G.; Willett, C.G.; Wright, C.D.; McMillian, N.R.; Pluchino, L.A. Esophageal and esophagogastric junction cancers, version 2.2019, NCCN clinical practice guidelines in oncology. J. Natl. Compr. Canc. Netw., 2019, 17(7), 855-883. doi: 10.6004/jnccn.2019.0033 PMID: 31319389
  9. Ma, R.; Yang, F.; Huang, D.; Zheng, M.; Wang, Y. The prognostic value of the expression of SMC4 mRNA in breast cancer. Dis. Markers, 2019, 2019, 1-7. doi: 10.1155/2019/2183057 PMID: 31871499
  10. Peng, L.; Tang, Y.; Zhang, Y.; Guo, S.; Peng, L.; Ye, L.; Wang, Y.; Jiang, Y. Structural maintenance of chromosomes 4 is required for leukemia stem cell maintenance in MLL-AF9 induced acute myeloid leukemia. Leuk. Lymphoma, 2018, 59(10), 2423-2430. doi: 10.1080/10428194.2017.1387906 PMID: 29043883
  11. Zhou, B.; Yuan, T.; Liu, M.; Liu, H.; Xie, J.; Shen, Y.; Chen, P. Overexpression of the structural maintenance of chromosome 4 protein is associated with tumor de-differentiation, advanced stage and vascular invasion of primary liver cancer. Oncol. Rep., 2012, 28(4), 1263-1268. doi: 10.3892/or.2012.1929 PMID: 22842912
  12. Feng, X.D.; Song, Q.; Li, C.W.; Chen, J.; Tang, H.M.; Peng, Z.H.; Wang, X.C. Structural maintenance of chromosomes 4 is a predictor of survival and a novel therapeutic target in colorectal cancer. Asian Pac. J. Cancer Prev., 2014, 15(21), 9459-9465. doi: 10.7314/APJCP.2014.15.21.9459 PMID: 25422241
  13. Zhang, C.; Kuang, M.; Li, M.; Feng, L.; Zhang, K.; Cheng, S. SMC4, which is essentially involved in lung development, is associated with lung adenocarcinoma progression. Sci. Rep., 2016, 6(1), 34508. doi: 10.1038/srep34508 PMID: 27687868
  14. Jiang, L.; Zhou, J.; Zhong, D.; Zhou, Y.; Zhang, W.; Wu, W.; Zhao, Z.; Wang, W.; Xu, W.; He, L.; Ma, Y.; Hu, Y.; Zhang, W.; Li, J. Overexpression of SMC4 activates TGFβ/Smad signaling and promotes aggressive phenotype in glioma cells. Oncogenesis, 2017, 6(3), e301. doi: 10.1038/oncsis.2017.8 PMID: 28287612
  15. Abdi, E.; Latifi-Navid, S.; Zahri, S.; Yazdanbod, A.; Pourfarzi, F. Risk factors predisposing to cardia gastric adenocarcinoma: Insights and new perspectives. Cancer Med., 2019, 8(13), 6114-6126. doi: 10.1002/cam4.2497 PMID: 31448582
  16. Chevallay, M.; Bollschweiler, E.; Chandramohan, S.M.; Schmidt, T.; Koch, O.; Demanzoni, G.; Mönig, S.; Allum, W. Cancer of the gastroesophageal junction: A diagnosis, classification, and management review. Ann. N. Y. Acad. Sci., 2018, 1434(1), 132-138. doi: 10.1111/nyas.13954 PMID: 30138540
  17. Chen, Y.; Huang, F. Deng; Yuan, X.; Tao, Q.; Wang, T.; Li, D.; Fan, Y.; Peng, Q.; Tang, D. HIF-1-miR-219-SMC4 regulatory pathway promoting proliferation and migration of HCC under hypoxic condition. BioMed Res. Int., 2019, 2019, 1-9. doi: 10.1155/2019/8983704 PMID: 31828143
  18. Zhou, J.; Wu, G.; Tong, Z.; Sun, J.; Su, J.; Cao, Z.; Luo, Y.; Wang, W. Prognostic relevance of SMC family gene expression in human sarcoma. Aging, 2021, 13(1), 1473-1487. doi: 10.18632/aging.202455 PMID: 33460400
  19. Dongre, A.; Weinberg, R.A. New insights into the mechanisms of epithelial–mesenchymal transition and implications for cancer. Nat. Rev. Mol. Cell Biol., 2019, 20(2), 69-84. doi: 10.1038/s41580-018-0080-4 PMID: 30459476
  20. Santamaria, P.G.; Moreno-Bueno, G.; Portillo, F.; Cano, A. EMT: Present and future in clinical oncology. Mol. Oncol., 2017, 11(7), 718-738. doi: 10.1002/1878-0261.12091 PMID: 28590039
  21. Zhang, Y.; Weinberg, R.A. Epithelial-to-mesenchymal transition in cancer: complexity and opportunities. Front. Med., 2018, 12(4), 361-373. doi: 10.1007/s11684-018-0656-6 PMID: 30043221
  22. Zhang, X.; Zhu, M.; Wang, H.; Song, Z.; Zhan, D.; Cao, W.; Han, Y.; Jia, J. Overexpression of NCAPG inhibits cardia adenocarcinoma apoptosis and promotes epithelial-mesenchymal transition through the Wnt/β-catenin signaling pathway. Gene, 2021, 766, 145163. doi: 10.1016/j.gene.2020.145163 PMID: 32980450
  23. Taciak, B.; Pruszynska, I.; Kiraga, L.; Bialasek, M.; Krol, M. Wnt signaling pathway in development and cancer. J. Physiol. Pharmacol., 2018, 69(2), 185-196. doi: 10.26402/jpp.2018.2.07 PMID: 29980141
  24. Shang, S.; Hua, F.; Hu, Z.W. The regulation of β-catenin activity and function in cancer: Therapeutic opportunities. Oncotarget, 2017, 8(20), 33972-33989. doi: 10.18632/oncotarget.15687 PMID: 28430641
  25. Tian, S.; Peng, P.; Li, J.; Deng, H.; Zhan, N.; Zeng, Z.; Dong, W. SERPINH1 regulates EMT and gastric cancer metastasis via the Wnt/β-catenin signaling pathway. Aging, 2020, 12(4), 3574-3593. doi: 10.18632/aging.102831 PMID: 32091407
  26. Wang, J.; Cai, H.; Liu, Q.; Xia, Y.; Xing, L.; Zuo, Q.; Zhang, Y.; Chen, C.; Xu, K.; Yin, P.; Chen, T. Cinobufacini inhibits colon cancer invasion and metastasis via suppressing Wnt/β-catenin signaling pathway and EMT. Am. J. Chin. Med., 2020, 48(3), 703-718. doi: 10.1142/S0192415X20500354 PMID: 32329642

Дополнительные файлы

Доп. файлы
Действие
1. JATS XML

© Bentham Science Publishers, 2024