SOX4在子宫内膜癌组织中的表达及其生物学作用

doi:10.16098/j.issn.0529-1356.2021.03.015

摘要/Abstract

摘要：

目的探讨性别决定区Y框蛋白4（SOX4）在子宫内膜癌组织中的表达水平及其生物学作用。方法收集156例子宫内膜癌组织和子宫内膜癌癌旁组织，另取156例子宫内膜不典型增生组织，采用免疫组织化学法检测子宫内膜癌、子宫内膜不典型增生和癌旁组织中SOX4的表达，并分析SOX4表达与子宫内膜癌患者临床特征的关系。采用慢病毒转染的技术方法建立SOX4过表达/沉默Ishikawa细胞株后，MTT、流式细胞术和Transwell小室法检测细胞的增殖、凋亡、迁移和侵袭能力，Western blotting检测SOX4、β-连环蛋白(β-catenin)和上皮型钙黏附蛋白(E-cadherin)的表达变化。结果 SOX4在子宫内膜癌组织中的表达高于癌旁组织和子宫内膜不典型增生组织(P<0.05)。SOX4表达与侵袭深度、国际妇产科联合会（FIGO）分期和淋巴结转移相关(P<0.05)。与对照组相比，SOX4过表达的Ishikawa细胞的增殖能力、迁移和侵袭能力显著增加，细胞凋亡率明显降低，蛋白SOX4和β-catenin表达水平明显升高，蛋白E-cadherin表达水平明显降低(均P<0.05)。SOX4干扰的Ishikawa细胞的增殖能力、迁移和侵袭能力显著降低，细胞凋亡率明显升高，蛋白SOX4和β-catenin表达水平明显降低，蛋白E-cadherin表达水平明显升高(均P<0.05)。结论 SOX4在子宫内膜癌组织中高表达，可能通过激活Wnt/β-catenin信号通路促进子宫内膜癌的发生发展。

关键词: SOX4, 子宫内膜癌, 迁移, 侵袭, Wnt/β-连环蛋白, 免疫印迹法, 人

Abstract:

Objective To investigate the expression of sex determining region Y box protein 4(SOX4) gene and its biological effects in endometrial carcinoma. Methods 156 cases of endometrial carcinoma tissues, adjacent tissues of endometrial carcinoma and 156 cases of endometrial atypical hyperplasia were collected; Immunohistochemistry was used to detect the expression of SOX4 in endometrial cancer, endometrial dysplasia and normal endometrial tissue, and to analyze the relationship between SOX4 and the clinical characteristics of patients with endometrial cancer. After establishing the SOX4 overexpression/silencing Ishikawa cell strain using the lentivirus transfection technique, MTT, flow cytometry and Transwell chamber method were used to detect the cell proliferation, apoptosis, migration and invasion ability, and Western blotting method was used to detect SOX4, βcatenin and E-cadherin protein expression changes. Results The expression of SOX4 in endometrial cancer tissue was higher than that in normal endometrial tissue and endometrial atypical hyperplasia (P<0.05). SOX4 expression was correlated with invasion depth, International Federation of Obstetrics and Gynecoogy(FIGO) stage and lymph node metastasis (P<0.05). Compared with control group, SOX4 overexpressed Ishikawa cells have significantly increased proliferative ability, migration and invasion ability, significantly reduced apoptosis rate, significantly increased SOX4 and β-catenin protein expression, and significantly reduced E-cadherin protein expression (all P<0.05). while the proliferation ability, migration and invasion ability of Ishikawa cells interfered by SOX4 were significantly reduced, the apoptosis rate was significantly increased, the expression of SOX4 and β-catenin protein was significantly reduced, and the expression of E-cadherin protein was significantly increased (all P<0.05). Conclusion SOX4 gene is highly expressed in endometrial cancer tissues, which may promote the development of endometrial cancer by activating Wnt/β-catenin signaling pathway.

Key words: Sex-determining region Y-box 4, Endometrial cancer, Migration, Invasion, Wnt/β-catenin, Western blotting, Human

中图分类号:

R737.33

刘佳淑范波黄锦刘胜凤. SOX4在子宫内膜癌组织中的表达及其生物学作用[J]. 解剖学报, 2021, 52(3): 425-431.

LIU Jia-shu FAN Bo HUANG Jin LIU Sheng-feng. Expression of SOX4 gene and its biological effects in endometrial carcinoma[J]. Acta Anatomica Sinica, 2021, 52(3): 425-431.

参考文献

［1］ Cui PH, Zhang YJ, Shao XZh, et al. Effect of overexpression of human epididymal protein 4 on proliferation, invasion and tumorigenesis of endometrial carcinoma cells［J］. Acta Anatomica Sinica, 2017, 48(6):704-709. (in Chinese)

崔彭华, 张玉娟, 邵雪斋, 等. 人附睾蛋白4过表达对子宫内膜癌细胞增殖、侵袭能力及肿瘤形成的影响［J］. 解剖学报, 2017, 48(6):704-709.

［2］ Li Y, Hao J, Jiang YM, et al. Long non-coding RNA DSCAM-AS1 indicates a poor prognosis and modulates cell proliferation, migration and invasion in ovarian cancer via upregulating SOX4［J］. Eur Rev Med Pharmacol Sci, 2019, 23(10):4143-4148.

［3］ Cheng Q, Du J, Xie L, et al. Inhibition of SOX4 induces melanoma cell apoptosis via downregulation of NF-κB p65 signaling［J］. Oncol Rep, 2018, 40(1):369-376.

［4］ Xu JW, Wu YH, Xia DJ, et al. Female reproductive toxicity of environmental endocrine disruptors and their roles in development and progression of gynecological tumors［J］. Journal of Environmental & Occupational Medicine, 2019, 36(1):50-56. (in Chinese)

徐嘉蔚, 吴一华, 夏大静. 环境内分泌干扰物的女性生殖毒性及其在妇科肿瘤发生发展中的作用［J］.环境与职业医学, 2019, 36(1):50-56.

［5］ Karlsson T, Krakstad C, Tangen IL, et al. Endometrial cancer cells exhibit high expression of p110β and its selective inhibition induces variable responses on PI3K signaling, cell survival and proliferation［J］. Oncotarget, 2017, 8(3):3881-3894.

［6］ Xiao YY, Lin L, Li YH, et al. ZEB1 promotes invasion and metastasis of endometrial cancer by interacting with HDGF and inducing its transcription［J］. Am J Cancer Res, 2019, 9(11):2314-2330

［7］ Tong Z, Liu Y, Yu X, et al. The transcriptional co-activator NCOA6 promotes estrogen-induced GREB1 transcription by recruiting ERα and enhancing enhancer-promoter interactions［J］. J Biol Chem, 2019, 294(51):19667-19682.

［8］ Vervoort SJ, van Boxtel R, Coffer PJ. The role of SRY-related HMG box transcription factor 4 (SOX4) in tumorigenesis and metastasis: friend or foe［J］. Oncogene, 2013, 32(29):3397-3409.

［9］ Xi J, Feng J, Zeng S. Long noncoding RNA lncBRM facilitates the proliferation, migration and invasion of ovarian cancer cells via upregulation of Sox4［J］. Am J Cancer Res, 2017, 7(11):2180-2189.

［10］ Zhang J, Jiang H, Shao J, et al. SOX4 inhibits GBM cell growth and induces G0/G1 cell cycle arrest through Akt-p53 axis［J］. BMC Neurol, 2014, 14:207.

［11］ Du Q, Liu J, Zhang X, et al. Propofol inhibits proliferation, migration, and invasion but promotes apoptosis by regulation of Sox4 in endometrial cancer cells［J］. Braz J Med Biol Res, 2018, 51(4):e6803.

［12］ Wang F, Liu L, Gao WQ, et al. Activation of Wnt/β-catenin signaling enhanced stemness of prostate cancer cells［J］. Tumor, 2019, 39(7):525-533. (in Chinese)

王凡, 刘林, 高维强. 前列腺癌细胞中Wnt/β-catenin信号通路激活可增强细胞干性［J］. 肿瘤, 2019, 39(7):525-533.

［13］ Xu XW, Yang YL, Sun ZhL, et al. Raptor promoting invasion and metastasis of breast cancer through the signaling pathway Wnt3a/β-catenin［J］. Acta Anatomica Sinica, 2017, 48(6):682-687. (in Chinese)

徐新伟, 杨玉玲, 孙志亮, 等. Raptor通过Wnt3a/β-catenin信号通路对乳腺癌侵袭与转移的作用［J］. 解剖学报, 2017, 48(6):682-687.

［14］ Chen X, Zhang L, Zhang T, et al. Methylation-mediated repression of microRNA 129-2 enhances oncogenic SOX4 expression in HCC［J］. Liver Int, 2013, 33(3):476-486.

［15］ Wang C, Zi H, Wang Y, et al. LncRNA CASC15 promotes tumour progression through SOX4/Wnt/β-catenin signalling pathway in hepatocellular carcinoma［J］.Artif Cells Nanomed Biotechnol, 2020, 48(1):763-769.

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