SRSF3调控CTLA-4外显子3的可变剪接的研究

doi:10.13701/j.cnki.kqyxyj.2019.01.022

口腔医学研究 ›› 2019, Vol. 35 ›› Issue (1): 94-97.DOI: 10.13701/j.cnki.kqyxyj.2019.01.022

SRSF3调控CTLA-4外显子3的可变剪接的研究

黄珺, 郭继华, 樊明文^*

武汉大学口腔医学院,湖北省口腔基础医学重点实验室-省部共建国家重点实验室培育基地, 口腔生物医学教育部重点实验室湖北武汉 430079

收稿日期:2018-07-27 出版日期:2019-01-18 发布日期:2019-01-28
通讯作者: 樊明文,E-mail:fmwmail@whu.edu.cn
作者简介:黄珺(1992~ ),女,湖北武汉人,硕士,主要从事牙体牙髓龋病学相关研究和临床工作。
基金资助:
国家自然科学基金(编号:81570972)

Alternative Splicing of CTLA-4 Exon3 is Regulated by SRSF3

HUANG Jun, GUO Ji-hua, FAN Ming-wen^*

The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China

Received:2018-07-27 Online:2019-01-18 Published:2019-01-28

摘要/Abstract

摘要： 目的:研究在肿瘤中高表达的可变剪接因子SRSF3对肿瘤免疫治疗相关因子CTLA-4外显子3的可变剪接的调控作用。方法:在人胚胎肾上皮细胞293细胞中分别共转染CTLA-4模拟基因和SRSF3特异性siRNA,CTLA-4模拟基因和SRSF3过表达质粒来敲低和过表达SRSF3,然后用逆转录PCR检测SRSF3敲低和过表达后对CTLA-4的两种可变剪接亚型,跨膜型CTLA-4(flCTLA-4)和可溶性CTLA-4(sCTLA-4)表达的影响。结果:在293细胞中抑制SRSF3的表达时,flCTLA-4可变剪接亚型的表达增加,sCTLA-4可变剪接亚型的表达降低,在293细胞中过表达SRSF3时,得到了相反的结果。结论:SRSF3作为肿瘤中高表达的原癌基因参与调控CTLA-4外显子3的可变剪接,并使flCTLA-4可变剪接亚型的表达降低,sCTLA-4可变剪接亚型的表达增加。

关键词: SRSF3, CTLA-4, 可变剪接

Abstract: Objective: To investigate the effects of SRSF3 on alternative splicing of CTLA-4 exon3. Methods: CTLA-4 minigene was co-transfected with SRSF3 siRNA and SRSF3 plasmid in human embryonic renal epithelial cells (293 cell) respectively to knock down and overexpress the expression of SRSF3. The effects on CTLA-4 splicing isoforms flCTLA-4 and sCTLA-4 were analyzed by RT-PCR. Results: Knock down of SRSF3 increased the expression of flCTLA-4 and inhibited sCTLA-4 product in 293 cells. Overexpression of SRSF3 showed the contrary result. Conclusion: SRSF3 regulates the alternative splicing of CTLA-4 exon 3, down-regulates the expression of flCTLA-4, and increases the expression of sCTLA-4 in human embryonic renal epithelial cells.

Key words: SRSF3, CTLA-4, Alternative splicing

黄珺, 郭继华, 樊明文. SRSF3调控CTLA-4外显子3的可变剪接的研究[J]. 口腔医学研究, 2019, 35(1): 94-97.

HUANG Jun, GUO Ji-hua, FAN Ming-wen. Alternative Splicing of CTLA-4 Exon3 is Regulated by SRSF3[J]. Journal of Oral Science Research, 2019, 35(1): 94-97.

参考文献

[1] Ward FJ, Dahal LN, Khanolkar RC, et al. Targeting the alternatively spliced soluble isoform of CTLA-4: prospects for immunotherapy [J]. Immunotherapy, 2014, 6(10): 1073-1084.
[2] Dunn GP, Old LJ, Schreiber RD. The three Es of cancer immunoediting [J]. Annu Rev Immunol, 2004, 22: 329-360.
[3] Snyder A, Makarov V, Merghoub T, et al. Genetic basis for clinical response to CTLA-4 blockade in melanoma [J]. N Engl J Med, 2014, 371(23): 2189-2199.
[4] Grosso JF, Jure-Kunkel MN. CTLA-4 blockade in tumor models: an overview of preclinical and translational research [J]. Cancer Immun, 2013, 13: 5.
[5] Gerold KD, Zheng P, Rainbow DB, et al. The soluble CTLA-4 splice variant protects from type 1 diabetes and potentiates regulatory T-cell function [J]. Diabetes, 2011, 60(7): 1955-1963.
[6] Corbo C, Orru S, Salvatore F. SRp20: an overview of its role in human diseases [J]. Biochem Biophys Res Commun, 2013, 436(1): 1-5.
[7] 刘佩琦,石黎明,贾荣.SRSF3调控口腔癌细胞中SPAG5外显子3的可变剪切的研究[J].口腔医学研究,2016,32(1): 8-11.
[8] 郭继华,贾荣.SRp20对口腔癌细胞丙酮酸激酶前体mRNA可变剪切的调控作用[J].武汉大学学报(医学版),2014,35(1): 8-10.
[9] Peggs KS, Quezada SA, Allison JP. Cancer immunotherapy: co-stimulatory agonists and co-inhibitory antagonists [J]. Clin Exp Immunol, 2009, 157(1): 9-19.
[10] Callahan MK, Wolchok JD. At the bedside: CTLA-4- and PD-1-blocking antibodies in cancer immunotherapy [J]. J Leukoc Biol, 2013, 94(1): 41-53.
[11] Aggarwal S, Sharma SC, N Das S. Dynamics of regulatory T cells (Tregs ) in patients with oral squamous cell carcinoma [J]. J Surg Oncol, 2017, 116(8): 1103-1113.
[12] Wang J, Xie T, Wang B, et al. PD-1 blockade prevents the development and progression of carcinogen-induced oral premalignant lesions [J]. Cancer Prev Res (Phila), 2017, 10(12): 684-693.
[13] Wu L, Deng WW, Huang CF, et al. Expression of VISTA correlated with immunosuppression and synergized with CD8 to predict survival in human oral squamous cell carcinoma [J]. Cancer Immunol Immunother, 2017, 66(5): 627-636.
[14] Kammerer PW, Toyoshima T, Schoder F, et al. Association of T-cell regulatory gene polymorphisms with oral squamous cell carcinoma [J]. Oral Oncol, 2010, 46(7): 543-548.
[15] Oaks MK, Hallett KM, Penwell RT, et al. A native soluble form of CTLA-4 [J]. Cell Immunol, 2000, 201(2): 144-153.
[16] Saverino D, Simone R, Bagnasco M, et al. The soluble CTLA-4 receptor and its role in autoimmune diseases: an update [J]. Auto Immun Highlights, 2010, 1(2): 73-81.
[17] Oaks MK, Hallett KM. Cutting edge: a soluble form of CTLA-4 in patients with autoimmune thyroid disease [J]. J Immunol, 2000, 164(10): 5015-5018.
[18] AlFadhli S. Overexpression and secretion of the soluble CTLA-4 splice variant in various autoimmune diseases and in cases with overlapping autoimmunity [J]. Genet Test Mol Biomarkers, 2013, 17(4): 336-341.
[19] Gerold KD, Zheng P, Rainbow DB, et al. The soluble CTLA-4 splice variant protects from type 1 diabetes and potentiates regulatory T-cell function [J]. Diabetes, 2011, 60(7): 1955-1963.
[20] Erfani N, Razmkhah M, Ghaderi A. Circulating soluble CTLA4 (sCTLA4) is elevated in patients with breast cancer [J]. Cancer Invest, 2010, 28(8): 828-832.

SRSF3调控CTLA-4外显子3的可变剪接的研究

Alternative Splicing of CTLA-4 Exon3 is Regulated by SRSF3

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