SOX11 抑制食管癌细胞增殖和迁移的机制研究

doi:10.11904/j.issn.1002-3070.2020.01.004

Abstract

Abstract: Objective The aim of this study was to investigate the expression of the transcription factor SOX11 in esophageal cancer tissues and cell lines,the effects on proliferation and migration of esophageal cancer EC109 cells,and to explore its mechanism of action.Methods RT-qPCR and immunohistochemistry were used to analyze the expression of SOX11 in esophageal tissues and cell lines;SOX11 plasmids were transfected into low expression esophageal cancer cells(EC109,KYSE150,KYSE410 and KYSE510)and normal esophageal epithelial HEEC cells.The overexpression of SOX11 was confirmed in EC109 cells transfected with pcDNA3.1(+)-Flag-SOX11(the experimental group)and pcDNA3.1(+)-Flag-vector plasmid(the control group).CCK-8 and Transwell assays were used to analyze the effects of SOX11 on proliferation and migration of EC109 cells.RT-qPCR and Western blot assays were used to verify the effect of SOX11 on cell proliferation and migration of EC109 cells.Results Compared with esophageal epithelial tissues,the expression of SOX11 at levels of mRNA and protein was significantly down-regulated in esophageal cancer tissues;the down-regulated expression of SOX11 protein was associated with tumor grade(P=0.014),T stage(P=0.036)and lymph node metastasis(P=0.014).At the same time,compared with esophageal epithelial cells,the mRNA expression of SOX11 was down-regulated in esophageal cancer cells;the difference was statistically significant(P＜0.001).Compared with the control group(empty vector),the cell viability was significantly suppressed in EC109 cells after transfected with SOX11 mimics for 24,48 and 72 h(P＜0.05);the cell migration ability of EC109 cells was significantly inhibited in the experimental group(P＜0.001);Compared with the control group,active-β-catenin and its downstream genes were also significantly suppressed in the experimental group.Conclusion SOX11 is down-regulated in human esophageal cancer tissues and cancer cell lines,and may participate in the process of esophageal cancer by antagonizing the Wnt/β-catenin signaling pathway.

Key words: Esophageal cancer, SOX11, Tumor suppressor genes, Cell proliferation/migration, Wnt/β-catenin

CLC Number:

R735

ZHAO Nannan, QIN Wen, HAN Yonghuan, LU Jing, LI Yamin, XU Yajun. Effects of SOX11 on inhibiting proliferation and migration of esophageal cancer cells[J]. Journal of Practical Oncology, 2020, 34(1): 17-23.

0
/ / Recommend

Add to citation manager EndNote|Reference Manager|ProCite|BibTeX|RefWorks

URL: http://journal09.magtechjournal.com/Jwk3_syzlxzz/EN/10.11904/j.issn.1002-3070.2020.01.004

http://journal09.magtechjournal.com/Jwk3_syzlxzz/EN/Y2020/V34/I1/17

References

1 Qiu ZH,Zhang WW,Zhang HH,et al.Brucea javanica oil emulsion improves the effect of radiotherapy on esophageal cancer cells by inhibiting cyclin D1-CDK4/6 axis[J].World J Gastroenterol,2019,25(20):2463-2472.
2 Huang J,Liu H,Sun T,et al.Omeprazole prevents CDX2 and SOX9 expression by inhibiting hedgehog signaling in Barrett′s esophagus cells[J].Clin Sci(Lond),2019,133(3):483-495.
3 张茂祥,孙惠昕,宋冰冰.2008-2012年哈尔滨市道里区恶性肿瘤发病与死亡分析[J].实用肿瘤学杂志,2019,33(3):261-265.
4 Xu S,Yu J,Wang Z,et al.SOX11 promotes osteoarthritis through induction of TNF-α[J].Pathol Res Pract,2019,6(2):152442-152451.
5 Qin Y,Sun B,Zhang F,et al.Sox7 is involved in antibody-dependent endothelial cell activation and renal allograft injury via the Jagged1-Notch1 pathway[J].Exp Cell Res,2019,375(2):20-27.
6 Wurm A,Sock E,Fuchshofer R,et al.Anterior segment dysgenesis in the eyes of mice deficient for the high-mobility-group transcription factor Sox11[J].Exp Eye Res,2008,86(6):895-907.
7 Dictor M,Ek S,Sundberg M,et al.Strong lymphoid nuclear expression of SOX11 transcription factor defines lymphoblastic neoplasms,mantle cell lymphoma and Burkitt′s lymphoma[J].Haematologica,2009,94(11):1563-1568.
8 Hide T,Takezaki T,Nakatani Y,et al.Sox11 prevents tumorigenesis of glioma-initiating cells by inducing neuronal differentiation[J].Cancer Res,2009,69(20):7953-7959.
9 Petrakis G,Veloza L,Clot G,et al.Increased tumor angiogenesis in SOX11-positive mantle cell lymphoma[J].Histopathology,2019,7(2):281-291.
10 Xu J,Wang L,Li J,et al.SOX11-negative mantle cell lymphoma:clinicopathologic and prognostic features of 75 patients[J].Am J Surg Pathol,2019,43(5):710-716.
11 Jian J,Wang GY,Zhao J.Increased expression of sex determining region Y-box 11(SOX11)in cutaneous malignant melanoma[J].J Int Med Res,2013,41(4):1221-1227.
12 Shepherd JH,Uray IP,Mazumdar A,et al.The SOX11 transcription factor is a critical regulator of basal-like breast cancer growth,invasion,and basal-like gene expression[J].Oncotarget,2016,7(11):13106-13121.
13 Xu S,Dong Y,Huo Z,et al.SOX11:a potentially useful marker in surgical pathology:a systematic analysis of SOX11 expression in epithelial and non-epithelial tumours[J].Histopathology,2019,74(3):391-405.
14 Tosic N,Petrovic I,Grujicic NK,et al.Prognostic significance of SOX2,SOX3,SOX11,SOX14 and SOX18 gene expression in adult de novo acute myeloid leukemia[J].Leuk Res,2018,67(3):32-38.
15 Palomero J,Vegliante MC,Eguileor A,et al.SOX11 defines two different subtypes of mantle cell lymphoma through transcriptional regulation of BCL6[J].Leukemia,2016,30(7):1596-1599.
16 National Health Commission of The People′s Republic of China.Chinese guidelines for diagnosis and treatment of esophageal carcinoma 2018(English version)[J].Chin J Cancer Res,2019,31(2):223-258.
17 Fatima I,El-Ayachi I,Taotao L,et al.The natural compound Jatrophone interferes with Wnt/β-catenin signaling and inhibits proliferation and EMT in human triple-negative breast cancer[J].PLoS One,2017,12(12):e0189864.
18 Li C,Lyu J,Meng QH.MiR-93 Promotes Tumorigenesis and metastasis of non-small cell lung cancer cells by activating the PI3K/Akt pathway via inhibition of LKB1/PTEN/CDKN1A[J].J Cancer,2017,8(5):870-879.
19 You A,Fokas E,Wang LF,et al.Expression of the Wnt antagonist DKK3 is frequently suppressed in sporadic epithelial ovarian cancer[J].J Cancer Res Clin Oncol,2011,137(4):621-627.
20 Zhang S,Li S,Gao JL.Promoter methylation status of the tumor suppressor gene SOX11 is associated with cell growth and invasion in nasopharyngeal carcinoma[J].Cancer Cell Int,2013,13(1):109.
21 Soldini D,Valera A,Solé C,et al.Assessment of SOX11 expression in routine lymphoma tissue sections:characterization of new monoclonal antibodies for diagnosis of mantle cell lymphoma[J].Am J Surg Patho,2014,38(1):86-93.
22 Lu TX,Li JY,Xu W.The role of SOX11 in mantle cell lymphoma[J].Leuk Res,2013,37(11):1412-1419.
23 Gadi J,Jung SH,Lee MJ,et al.The transcription factor protein Sox11 enhances early osteoblast differentiation by facilitating proliferation and the survival of mesenchymal and osteoblast progenitors[J].J Biol Chem,2013,288(35):25400-25413.
24 Cizelsky W,Hempel A,Metzig M,et al.sox4 and sox11 function during Xenopus laevis eye development[J].PLoS One,2013,8(7):e69372.
25 Meggendorfer M,Kern W,Haferlach C,et al.SOX11 overexpression is a specific marker for mantle cell lymphoma and correlates with t(11;14)translocation,CCND1 expression and an adverse prognosis[J].Leukemia,2013,27(12):2388-23891.

[1]	QIN Wen,ZHAO Nannan,HAN Yonghuan,XU Yajun. Expression of ZNF436 in gastric cancer and its effect on the migration and invasion of gastric cancer cells by WNT/β-catenin [J]. PRACTICAL ONCOLOGY JOURNAL, 2019, 33(3): 222-227.
[2]	YUAN Guixia, LI Yan, FENG Wanqi, XIA Xiaojuan, LI Xu. Mechanism of tumor suppressor gene DKK2 inhibiting proliferation of nephroblastoma cells in children [J]. PRACTICAL ONCOLOGY JOURNAL, 2019, 33(1): 14-20.
[3]	LIU Zhongyang, YUAN Xin, ZHOU Wen, LI Xiaoliang, FAN Limao. Therapeutic effect of minimally invasive small incision surgery on patients with early thoracic esophageal cancer and its influence in pain [J]. PRACTICAL ONCOLOGY JOURNAL, 2019, 33(1): 57-61.
[4]	YU Fang, ZHAO Pei. The role and mechanism of TRAP1 in the development of esophageal cancer [J]. PRACTICAL ONCOLOGY JOURNAL, 2018, 32(6): 515-519.
[5]	DU Lingbin,WEI Wenqiang. Progress research in survival analysis of esophageal squamous cell carcinoma(ESCC)in Chinese population [J]. PRACTICAL ONCOLOGY JOURNAL, 2018, 32(4): 344-348.
[6]	JIN Jing,HE Yutong. Research progress of miR-21 in esophageal cancer [J]. PRACTICAL ONCOLOGY JOURNAL, 2017, 31(3): 277-280.
[7]	GAO Shile,HU Zongtao,DONG Liuyi,WANG Chong,LV Donglai,ZHENG Chun. One case on esophageal cancer accompanied with eyeball and liver metastasis [J]. PRACTICAL ONCOLOGY JOURNAL, 2015, 29(4): 347-349.
[8]	QIU Zidan,LI Jiancheng. Molecular targeted therapy for esophageal cancer [J]. PRACTICAL ONCOLOGY JOURNAL, 2015, 29(1): 57-60.
[9]	TANG Xiaojun,LIU Gaohua,WANG Xiaoyong,ZHAN Fusheng. Effect of mediastinal drainage on treatment of intra-thoracic anastomotic leak in post operation of esophageal cancer patients [J]. PRACTICAL ONCOLOGY JOURNAL, 2014, 28(6): 535-539.
[10]	YIN Hongtao,E Mingyan,WANG Muhong,ZHANG Yan. Clinical factors and their curative effect analysis in elderly esophageal cancer patients with radiotherapy [J]. PRACTICAL ONCOLOGY JOURNAL, 2012, 26(3): 236-240.
[11]	ZHANG Yuxue,WU Haiyan,LI Huiyan. The meta-analysis between p53 alteration and smoking,alcohol consumption in esophageal cancer among Chinese population [J]. PRACTICAL ONCOLOGY JOURNAL, 2011, 25(4): 315-318.
[12]	WU Yan, ZHANG Yan, XU Ji, LU Yingzhi. Evaluation of combined docetaxel and nedaplatin chemotherapy for advanced esophageal cancer [J]. PRACTICAL ONCOLOGY JOURNAL, 2010, 24(1): 38-40.
[13]	WANG Jian, SUN Suping, ZHANG Xuguang, NI Xinchu, YU Jingping, LI Yi. Side effects contrasting of nedaplatin plus 5-Fu and cisplatin plus 5-Fu combined with synchronous radiotherapy on esophageal cancer [J]. PRACTICAL ONCOLOGY JOURNAL, 2009, 23(6): 513-515.
[14]	GAO Fei, JIA Lin, DU Huizhang, WANG Yun, KUANG Xiaohong, HAN Jianjun. A clinical study of combination of radiotherapy and IP regimen in the treatment of patients with local advanced esophageal cancer [J]. PRACTICAL ONCOLOGY JOURNAL, 2009, 23(2): 126-129.

Effects of SOX11 on inhibiting proliferation and migration of esophageal cancer cells

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 14

Recommended Articles

Metrics

Comments