High expression of spermatogenesis associated serine rich 2 promotes tumorigenicity in esophageal squamous cell carcinoma cells and is associated with poor patient prognosis

Liu,Yan-Peng; Cao,Qiuhong; Li,Ling; Zhang,Min

doi:10.3892/etm.2021.10130

High expression of spermatogenesis associated serine rich 2 promotes tumorigenicity in esophageal squamous cell carcinoma cells and is associated with poor patient prognosis

Authors:
- Yan-Peng Liu
- Qiuhong Cao
- Ling Li
- Min Zhang
View Affiliations

Affiliations: Department of Internal Medicine, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China, Department of Anesthesiology, Jinan Central Hospital, Jinan, Shandong 250013, P.R. China, Department of Thoracic Surgery, Affiliated Hospital of Shandong Academy of Medical Sciences, Jinan, Shandong 250031, P.R. China
Published online on: May 2, 2021 https://doi.org/10.3892/etm.2021.10130
Article Number: 698
Copyright: © Liu 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

Spermatogenesis associated serine rich 2 (SPATS2), recognized as a cytoplasmic RNA‑binding protein, is implicated in the tumorgenicity of several cancers. However, the potential role of SPATS2 in esophageal squamous cell carcinoma (ESCC) is yet to be elucidated. The present study aimed to explore the functional implication of SPATS2 in ESCC. The ESCC cell lines Eca109 and KYSE‑150 were used to conduct loss‑of‑function experiments. The expression patterns of SPATS2 in patients with ESCC were obtained from Oncomine, The Cancer Genome Atlas and Genotype‑Tissue Expression databases. Reverse transcription‑quantitative PCR and western blot analysis were applied to determine the expression levels of SPATS2 in ESCC cells. The proliferation of ESCC cells was measured via cell proliferation and colony‑formation assays. Subsequently, the migration and invasion capacities of ESCC cells were observed using Transwell assays. Finally, the expression levels of P53, cyclin E, matrix metalloproteinase (MMP)‑9 and neuronal‑cadherin were determined via western blot analysis. SPATS2 was expressed at higher levels in ESCC tissues compared with the controls, and high expression of SPATS2 was associated with poor prognosis. ESCC cell line proliferation, migration and invasion abilities were suppressed after silencing SPATS2. Moreover, following knockdown of SPATS2, the proteins cyclin E, MMP‑9 and N‑cadherin were expressed at markedly decreased levels, while P53 expression was increased. In summary, the results of the present study suggest that SPATS2 promotes ESCC development and progression, providing potential insights into future ESCC targeted treatment.

View Figures

View References

1	Hu JM, Liu K, Liu JH, Jiang XL, Wang XL, Chen YZ, Li SG, Zou H, Pang LJ, Liu CX, et al: CD163 as a marker of M2 macrophage, contribute to predict aggressiveness and prognosis of Kazakh esophageal squamous cell carcinoma. Oncotarget. 8:21526–21538. 2017.PubMed/NCBI View Article : Google Scholar
2	Sakai NS, Samia-Aly E, Barbera M and Fitzgerald RC: A review of the current understanding and clinical utility of miRNAs in esophageal cancer. Semin Cancer Biol. 23:512–521. 2013.PubMed/NCBI View Article : Google Scholar
3	Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015.PubMed/NCBI View Article : Google Scholar
4	Murphy G, McCormack V, Abedi-Ardekani B, Arnold M, Camargo MC, Dar NA, Dawsey SM, Etemadi A, Fitzgerald RC, Fleischer DE, et al: International cancer seminars: A focus on esophageal squamous cell carcinoma. Ann Oncol. 28:2086–2093. 2017.PubMed/NCBI View Article : Google Scholar
5	Gao S, Li S, Duan X, Gu Z, Ma Z, Yuan X, Feng X and Wang H: Inhibition of glycogen synthase kinase 3 beta (GSK3beta) suppresses the progression of esophageal squamous cell carcinoma by modifying STAT3 activity. Mol Carcinog. 56:2301–2316. 2017.PubMed/NCBI View Article : Google Scholar
6	Wang C, Wang J, Chen Z, Gao Y and He J: Immunohistochemical prognostic markers of esophageal squamous cell carcinoma: A systematic review. Chin J Cancer. 36(65)2017.PubMed/NCBI View Article : Google Scholar
7	Ekman S, Dreilich M, Lennartsson J, Wallner B, Brattstrom D, Sundbom M and Bergqvist M: Esophageal cancer: Current and emerging therapy modalities. Expert Rev Anticancer Ther. 8:1433–1448. 2008.PubMed/NCBI View Article : Google Scholar
8	Senoo M, Hoshino S, Mochida N, Matsumura Y and Habu S: Identification of a novel protein p59(scr), which is expressed at specific stages of mouse spermatogenesis. Biochem Biophys Res Commun. 292:992–998. 2002.PubMed/NCBI View Article : Google Scholar
9	Damas ND, Marcatti M, Come C, Christensen LL, Nielsen MM, Baumgartner R, Gylling HM, Maglieri G, Rundsten CF, Seemann SE, et al: SNHG5 promotes colorectal cancer cell survival by counteracting STAU1-mediated mRNA destabilization. Nat Commun. 7(13875)2016.PubMed/NCBI View Article : Google Scholar
10	Ngollo M, Lebert A, Daures M, Judes G, Rifai K, Dubois L, Kemeny JL, Penault-Llorca F, Bignon YJ, Guy L and Bernard-Gallon D: Global analysis of H3K27me3 as an epigenetic marker in prostate cancer progression. BMC Cancer. 17(261)2017.PubMed/NCBI View Article : Google Scholar
11	Takamochi K, Ohmiya H, Itoh M, Mogushi K, Saito T, Hara K, Mitani K, Kogo Y, Yamanaka Y, Kawai J, et al: Novel biomarkers that assist in accurate discrimination of squamous cell carcinoma from adenocarcinoma of the lung. BMC Cancer. 16(760)2016.PubMed/NCBI View Article : Google Scholar
12	Zhu CH, Kim J, Shay JW and Wright WE: SGNP: An essential Stress Granule/Nucleolar Protein potentially involved in 5.8s rRNA processing/transport. PLoS One. 3(e3716)2008.PubMed/NCBI View Article : Google Scholar
13	Donati G, Montanaro L and Derenzini M: Ribosome biogenesis and control of cell proliferation: p53 is not alone. Cancer Res. 72:1602–1607. 2012.PubMed/NCBI View Article : Google Scholar
14	Min P, Li W, Zeng D, Ma Y, Xu D, Zheng W, Tang F, Chen J, Shi J, Hu H, et al: A single nucleotide variant in microRNA-1269a promotes the occurrence and process of hepatocellular carcinoma by targeting to oncogenes SPATS2L and LRP6. Bull Cancer. 104:311–320. 2017.PubMed/NCBI View Article : Google Scholar
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. 25:402–8. 2001.PubMed/NCBI View Article : Google Scholar
16	Baba Y, Saeki H, Nakashima Y, Oki E, Shigaki H, Yoshida N, Watanabe M, Maehara Y and Baba H: Review of chemotherapeutic approaches for operable and inoperable esophageal squamous cell carcinoma. Dis Esophagus. 30:1–7. 2017.PubMed/NCBI View Article : Google Scholar
17	Seki K, Koshi R, Sugano N, Masutani S, Yoshinuma N and Ito K: Microarray analysis of bisphenol A-induced changes in gene expression in human oral epithelial cells. Acta Biochim Biophys Sin (Shanghai). 39:879–884. 2007.PubMed/NCBI View Article : Google Scholar
18	Cicenas J, Tamosaitis L, Kvederaviciute K, Tarvydas R, Staniute G, Kalyan K, Meskinyte-Kausiliene E, Stankevicius V and Valius M: KRAS, NRAS and BRAF mutations in colorectal cancer and melanoma. Med Oncol. 34(26)2017.PubMed/NCBI View Article : Google Scholar
19	Melo M, Gaspar da Rocha A, Batista R, Vinagre J, Martins MJ, Costa G, Ribeiro C, Carrilho F, Leite V, Lobo C, et al: TERT, BRAF, and NRAS in primary thyroid cancer and metastatic disease. J Clin Endocrinol Metab. 102:1898–1907. 2017.PubMed/NCBI View Article : Google Scholar
20	Giannou AD, Marazioti A, Kanellakis NI, Giopanou I, Lilis I, Zazara DE, Ntaliarda G, Kati D, Armenis V, Giotopoulou GA, et al: NRAS destines tumor cells to the lungs. EMBO Mol Med. 9:672–686. 2017.PubMed/NCBI View Article : Google Scholar
21	Li Y, Shan Z, Liu C, Yang D, Wu J, Men C and Xu Y: MicroRNA-294 promotes cellular proliferation and motility through the PI3K/AKT and JAK/STAT pathways by Upregulation of NRAS in bladder cancer. Biochemistry (Mosc). 82:474–482. 2017.PubMed/NCBI View Article : Google Scholar
22	De Amicis F, Perri A, Vizza D, Russo A, Panno ML, Bonofiglio D, Giordano C, Mauro L, Aquila S, Tramontano D and Ando S: Epigallocatechin gallate inhibits growth and epithelial-to-mesenchymal transition in human thyroid carcinoma cell lines. J Cell Physiol. 228:2054–2062. 2013.PubMed/NCBI View Article : Google Scholar
23	Bellini MF, Cadamuro AC, Succi M, Proenca MA and Silva AE: Alterations of the TP53 gene in gastric and esophageal carcinogenesis. J Biomed Biotechnol. 2012(891961)2012.PubMed/NCBI View Article : Google Scholar
24	Zhang Y, Zhu C, Sun B, Lv J, Liu Z, Liu S and Li H: Integrated high throughput analysis identifies GSK3 as a crucial determinant of p53-mediated apoptosis in lung cancer cells. Cell Physiol Biochem. 42:1177–1191. 2017.PubMed/NCBI View Article : Google Scholar
25	Dai L, Liu Y, Liu J, Wen X, Xu Z, Wang Z, Sun H, Tang S, Maguire AR, Quan J, et al: A novel cyclinE/cyclinA-CDK inhibitor targets p27(Kip1) degradation, cell cycle progression and cell survival: Implications in cancer therapy. Cancer Lett. 333:103–112. 2013.PubMed/NCBI View Article : Google Scholar
26	Huang L, Ren F, Tang R, Feng Z and Chen G: Prognostic value of expression of Cyclin E in gastrointestinal cancer: A systematic review and meta-analysis. Technol Cancer Res Treat. 15:12–19. 2016.PubMed/NCBI View Article : Google Scholar
27	Thaker PH, Han LY, Kamat AA, Arevalo JM, Takahashi R, Lu C, Jennings NB, Armaiz-Pena G, Bankson JA, Ravoori M, et al: Chronic stress promotes tumor growth and angiogenesis in a mouse model of ovarian carcinoma. Nat Med. 12:939–944. 2006.PubMed/NCBI View Article : Google Scholar
28	Grunwald B, Vandooren J, Locatelli E, Fiten P, Opdenakker G, Proost P, Kruger A, Lellouche JP, Israel LL, Shenkman L and Comes Franchini M: Matrix metalloproteinase-9 (MMP-9) as an activator of nanosystems for targeted drug delivery in pancreatic cancer. J Control Release. 239:39–48. 2016.PubMed/NCBI View Article : Google Scholar
29	Bai X, Li YY, Zhang HY, Wang F, He HL, Yao JC, Liu L and Li SS: Role of matrix metalloproteinase-9 in transforming growth factor-β1-induced epithelial-mesenchymal transition in esophageal squamous cell carcinoma. Onco Targets Ther. 10:2837–2847. 2017.PubMed/NCBI View Article : Google Scholar
30	Derycke LD and Bracke ME: N-cadherin in the spotlight of cell-cell adhesion, differentiation, embryogenesis, invasion and signalling. Int J Dev Biol. 48:463–476. 2004.PubMed/NCBI View Article : Google Scholar
31	Blaschuk OW: N-cadherin antagonists as oncology therapeutics. Philos Trans R Soc Lond B Biol Sci. 370(20140039)2015.PubMed/NCBI View Article : Google Scholar