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Vol. 66 No. 2: Issue 2

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TBRG4 silencing promotes progression of squamous cell carcinoma via regulation of CAV-1 expression and ROS formation

https://doi.org/10.14715/cmb/2020.66.2.26
Junqi Wang
Department of Thoracic Surgery, Baoji Central Hospital, Baoji 721008, China
Qing Luo
Department of Thoracic Surgery, Baoji Central Hospital, Baoji 721008, China
Mingwei Liu
Department of Thoracic Surgery, Baoji Central Hospital, Baoji 721008, China
Chao Zhang
Department of Thoracic Surgery, Baoji Central Hospital, Baoji 721008, China
Yong Jia
Department of Thoracic Surgery, Baoji Central Hospital, Baoji 721008, China
Ruifeng Tong
Department of Thoracic Surgery, Baoji Central Hospital, Baoji 721008, China
Litao Yang
Department of Thoracic Surgery, Baoji Central Hospital, Baoji 721008, China
Xiaowei Fu
Department of Thoracic Surgery, Baoji Central Hospital, Baoji 721008, China

Corresponding Author(s) : Junqi Wang

gmrgf4@163.com

Cellular and Molecular Biology, Vol. 66 No. 2: Issue 2

Abstract

Esophageal cancer is the eighth most common cancer globally. Transforming growth factor β regulator 4 (TBRG4) and caveolin-1 (CAV-1) are implicated in tumor progression. The aim of this study was to investigate the expressions of TBRG4 and CAV-1 in esophageal squamous cell carcinoma (ESCC), and their relationship with reactive oxygen species (ROS) formation. Human ESCC cell lines (EC9706, TE-1, and Eca109), and normal esophageal mucosal cell line (Het-1) were used in this study. The silencing of TBRG4 and/or CAV-1 by sh-RNA or overexpression of CAV-1 after TBRG4 knockdown was used to assess ROS levels. The results showed that down-regulation of TBRG4 reduced CAV-1 expression, and promoted ROS formation in ESCCs (p < 0.01). However, CAV-1 overexpression increased the expression level of TBRG4, but decreased ROS level in EC9706 cells (p < 0.01). Similarly, TBRG4 knockdown significantly reduced CAV-1 expression, promoted ROS formation, and caused cell cycle arrest at G0/G1 phase (p < 0.01). Caveolin-1 (CAV-1) knockdown also promoted cell apoptosis, cellular ROS formation and cell cycle arrest at G0/G1 phase (p < 0.01). However, CAV-1 overexpression in sh-TBRG4-treated EC9706 cells significantly upregulated TBRG4 expression, but significantly reduced the level of ROS, and inhibited cell-cycle arrest and apoptosis (p < 0.01). The enhancements in bcl-2/bax ratio, cytochrome c expression, and ROS levels by sh-TBRG4 were significantly reversed by CAV-1 overexpression in EC9706 cells. These results show that the upregulated expression of TBRG4 or CAV-1 promotes ESCC progression via regulation of intracellular ROS levels and inhibition of mitochondria-dependent apoptotic pathway.

Keywords

Esophageal cancer Caveolin-1 Reactive oxygen species Cell apoptosis Expression.
Wang, J., Luo, Q., Liu, M., Zhang, C., Jia, Y., Tong, R., Yang, L., & Fu, X. (2020). TBRG4 silencing promotes progression of squamous cell carcinoma via regulation of CAV-1 expression and ROS formation. Cellular and Molecular Biology, 66(2), 157–164. https://doi.org/10.14715/cmb/2020.66.2.26
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References
  1. Arnold M, Soerjomataram I, Ferlay J, Forman D. Global incidence of oesophageal cancer by histological subtype in 2012. Gut 2015; 64: 381-387.
  2. Simarro M, Gimenez-Cassina A, Kedersha N, Lazaro JB, Adelmant GO, Marto JA. Fast kinase domain-containing protein 3 is a mitochondrial protein essential for cellular respiration. Biochem Biophys Res Commun 2010; 401: 440-446.
  3. Sevcikova S, Paszekova H, Besse L, Sedlarikova L, Kubaczkova V, Almasi M, et al. Extramedullary relapse of multiple myeloma defined as the highest risk group based on deregulated gene expression data. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2015; 159: 288-293.
  4. Edwards MC, Liegeois N, Horecka J, DePinho RA, Sprague GF, Tyers M, et al. Human CPR (cell cycle progression restoration) genes impart a Far- phenotype on yeast cells. Genetics 1997; 147: 1063-1076.
  5. Wolf AR, Mootha VK. Functional genomic analysis of human mitochondrial RNA processing. Cell Rep 2014; 7: 918-931.
  6. Rolland T, Tasan M, Charloteaux B, Pevzner SJ, Zhong Q, Sahni N, et al. A proteome-scale map of the human interactome network. Cell 2014; 159: 1212-1226.
  7. Burgermeister E, Liscovitch M, Rocken C, Schmid RM, Ebert MP. Caveats of caveolin-1 in cancer progression. Cancer Lett 2008; 268: 187-201.
  8. Hu YC, Lam KY, Law S, Wong J, Srivastava G. Profiling of differentially expressed cancer-related genes in esophageal squamous cell carcinoma (ESCC) using human cancer cDNA arrays: overexpression of oncogene MET correlates with tumor differentiation in ESCC. Clin Cancer Res 2001; 7: 3519-3525.
  9. Kato K, Hida Y, Miyamoto M, Hashida H, Shinohara T, Itoh T, et al. Overexpression of caveolin-1 in esophageal squamous cell carcinoma correlates with lymph node metastasis and pathologic stage. Cancer 2002; 94: 929-933.
  10. Wang A, Zhao C, Liu X, Su W, Duan G, Xie Z, et al. Knockdown of TBRG4 affects tumorigenesis in human H1299 lung cancer cells by regulating DDIT3, CAV1 and RRM2. Oncol Lett 2018; 15: 121-128.
  11. Lei K, Tan S, Du W, Xu Y, Lin S, Zheng Y, et al. 3B, a novel of photosensitizer, exhibited anti-tumor effects via mitochondrial apoptosis pathway in MCF-7 human breast carcinoma cells. Tumour Biol 2015; 36: 5597-5606.
  12. Luanpitpong S, Talbott SJ, Rojanasakul Y, Nimmannit U, Pongrakhananon V, Wang L, et al. Regulation of lung cancer cell migration and invasion by reactive oxygen species and caveolin-1. J Biol Chem 2010; 285: 38832-38840.
  13. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 2001; 25: 402-408.
  14. Zhang X, Lan L, Niu L, Lu J, Li C, Guo M, et al. Oxidative stress regulates cellular bioenergetics in esophageal squamous cell carcinoma cell. Biosci Rep 2017; 37: 20171006.
  15. Robertson JD, Orrenius S, Zhivotovsky B. Review: nuclear events in apoptosis. J Struct Biol 2000; 129: 346-358.
  16. Zhang Y. Epidemiology of esophageal cancer. World J Gastroenterol 2013; 19: 5598-5606.
  17. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016, CA. Cancer J Clin 2016; 66: 7-30.
  18. Zeng H, Zheng R, Guo Y, Zhang S, Zou X, Wang N, et al. Cancer survival in China, 2003-2005: a population-based study. Int J Cancer 2015; 136: 1921-1930.
  19. DeAngelis R, Sant M, Coleman MP, Francisci S, Baili P, Pierannunzio D, et al. Cancer survival in Europe 1999-2007 by country and age: results of EUROCARE--5-a population-based study. Lancet Oncol 2014; 15: 23-34.
  20. Zaccagnino P, Saltarella M, D'Oria S, Corcelli A, Saponetti MS, Lorusso M, et al. N-arachidonylglycine causes ROS production and cytochrome c release in liver mitochondria. Free Radic Biol Med 2009; 47: 585-592.
  21. Lee JH, Won YS, Park KH, Lee MK, Tachibana H, Yamada K, et al. Celastrol inhibits growth and induces apoptotic cell death in melanoma cells via the activation ROS-dependent mitochondrial pathway and the suppression of PI3K/AKT signaling. Apoptosis 2012; 17: 1275-1286.
  22. Xie CM, Chan WY, Yu S, Zhao J, Cheng CH. Bufalin induces autophagy-mediated cell death in human colon cancer cells through reactive oxygen species generation and JNK activation. Free Radic Biol Med 2011; 51: 1365-1375.
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