SRSF1 promotes proliferation, invasion and migration of esophageal squamous cell carcinoma Eca9706 cells by regulating VEGFA mRNA alternative splicing

Yuqing DUAN; Ning XIA; Yunlong JIA; Wenya ZHENG; Lihua LIU

doi:10.19401/j.cnki.1007-3639.2022.03.001

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SRSF1 promotes proliferation, invasion and migration of esophageal squamous cell carcinoma Eca9706 cells by regulating VEGFA mRNA alternative splicing

Article | 更新时间：2025-12-31

- SRSF1 promotes proliferation, invasion and migration of esophageal squamous cell carcinoma Eca9706 cells by regulating VEGFA mRNA alternative splicing
- China Oncology Vol. 32, Issue 3, Pages: 191-199(2022)
- 作者机构：
  
  河北医科大学第四医院肿瘤免疫科,河北石家庄 050035
- 作者简介：
- 基金信息：
- DOI：10.19401/j.cnki.1007-3639.2022.03.001
  CLC： R735.1
- Received：01 December 2021，
  
  Published：30 March 2022
- 稿件说明：
移动端阅览
Yuqing DUAN, Ning XIA, Yunlong JIA, et al. SRSF1 promotes proliferation, invasion and migration of esophageal squamous cell carcinoma Eca9706 cells by regulating VEGFA mRNA alternative splicing[J]. China Oncology, 2022, 32(3): 191-199.
DOI：

Yuqing DUAN, Ning XIA, Yunlong JIA, et al. SRSF1 promotes proliferation, invasion and migration of esophageal squamous cell carcinoma Eca9706 cells by regulating VEGFA mRNA alternative splicing[J]. China Oncology, 2022, 32(3): 191-199. DOI： 10.19401/j.cnki.1007-3639.2022.03.001.

摘要

背景与目的：

丝氨酸/精氨酸富集剪接因子1（serine/arginine-rich splicing factor 1

SRSF1）与肿瘤的发生、发展密切相关。食管癌是常见的消化系统恶性肿瘤

但SRSF1在食管癌中的作用罕有报道。检测SRSF1在食管鳞状细胞癌（esophageal squamous cell carcinoma

ESCC）组织中的表达及其对ESCC细胞增殖、迁移和侵袭的影响

并初步探讨其作用机制。

方法：

收集2020年1月

#x02014;2021年12月于河北医科大学第四医院行手术切除的40例ESCC患者的癌及癌旁组织标本

采用免疫组织化学染色法检测ESCC组织中SRSF1的水平。采用实时荧光定量聚合酶链反应（real-time fluorescence quantitative polymerase chain reaction

RTFQ-PCR）和蛋白质印迹法（Western blot）检测ESCC细胞系中SRSF1 mRNA表达和蛋白水平。筛选SRSF1高表达的Eca9706细胞进行研究。采用小干扰RNA（small interfering RNA

siRNA）技术降低SRSF1 mRNA表达。采用细胞计数试剂盒-8（cell counting kit-8

CCK-8）、transwell和Matrigel基质胶实验分别检测Eca9706细胞增殖、迁移和侵袭能力。采用数据库分析ESCC组织中血管内皮生长因子A（vascular endothelial growth factor A

VEGFA）的表达

并分析SRSF1与VEGFA表达的相关性。采用RTFQ-PCR检测Eca9706细胞VEGFA Iso8a和Iso8b亚型的表达水平

以及敲低SRSF1后VEGFA Iso8a和Iso8b亚型的表达变化。

结果：

SRSF1在ESCC组织中的表达水平高于癌旁组织（

0.05）。SRSF1 mRNA表达和蛋白水平在ESCC Eca9706细胞系中最高（

0.01）。转染siRNA-SRSF1组中SRSF1 mRNA表达和蛋白水平显著低于siRNA-NC组（

0.01）。与siRNA-NC组相比

siRNA-SRSF1组Eca9706

细增殖、迁移和侵袭能力显著降低（

0.05）。ESCC组织中VEGFA表达明显高于食管正常组织（

0.05）

且与SRSF1表达呈正相关（

0.01）。Eca9706细胞VEGFA Iso8a亚型表达明显高于VEGFA Iso8b亚型（

0.01）

且敲低SRSF1后VEGFA Iso8a亚型表达降低

VEGFA Iso8b亚型表达升高（

0.01）。

结论：

SRSF1可通过作用于VEGFA可变剪接促进ESCC Eca9706细胞增殖、侵袭和迁移。

Abstract

Background and purpose:

Serine/arginine-rich splicing factor 1 (SRSF1) is closely related to the development of tumor. Esophageal carcinoma is the common malignant tumor of digestive system. However

the role of SRSF1 in esophageal carcinoma is rarely reported. This study aimed to detect the expression of SRSF1 in esophageal squamous cell carcinoma (ESCC) and its effects on the proliferation

invasion and migration of ESCC cells

and to explore its mechanism.

Methods:

Forty pairs of ESCC tissues and paracancerous tissues resected at the Fourth Hospital of Hebei Medical University from January 2020 to December 2021 were collected for this study. The expression of SRSF1 in ESCC was detected by immunohistochemistry. The mRNA expression and protein level of SRSF1 in ESCC cells were detected by real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) and Western blot

respectively. Eca9706 cell with high expression of SRSF1 was selected. The mRNA expression of SRSF1 was reduced by small interfering RNA (siRNA). The proliferation

migration and invasion of Eca9706 cells were detected by cell counting kit-8 (CCK-8)

transwell and Matrigel matrix gel assays

respectively. Database was used to analyze the expression of vascular endothelial growth factor A (VEGFA) in ESCC tissues

and the correlation between expressions of SRSF1 and VEGFA was also analyzed. RTFQ-PCR was used to detect the expression levels of VEGFA Iso8a and Iso8b isoform in Eca9706 cells

and the change in VEGFA Iso8a and Iso8b isoform expressions was also detected after knocking down SRSF1.

Results:

The expression of SRSF1 was significantly higher in ESCC tissues than in normal esophageal tissues (

0.05). SRSF1 mRNA and protein were highly expressed in Eca9706 cells (both

0.01). The mRNA expression and protein level of SRSF1 was significantly lower in siRNA-SRSF1 group than in siRNA-NC group (

0.01). After knocking down SRSF1

the proliferation

migration and invasion abilities of Eca9706 cells were significantly lower compared with siRNA-NC group (all

0.05). The expression of VEGFA was significantly higher in ESCC tissue than in normal esophageal tissue (

0.05)

and it was positively correlated with the expression of SRSF1 (

0.01). RTFQ-PCR showed that the level of VEGFA Iso8a expression in Eca9706 cells was significantly higher compared with VEGFA Iso8b (

0.01). Moreover

the level of VEGFA Iso8a expression was significantly decreased

while the level of VEGFA Iso8b expression increased after knocking down SRSF1 (

0.01).

Conclusion:

SRSF1 can promote proliferation

invasion and migration of ESCC Eca9706 cells by possibly regulating VEGFA mRNA splicing.

关键词

Keywords

references

BRAY F , FERLAY J , SOERJOMATARAM I , et al . Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries [J ] . CA Cancer J Clin , 2018 , 68 ( 6 ): 394 - 424 . DOI: 10.3322/caac.v68.6 http://doi.org/10.3322/caac.v68.6 http://doi.wiley.com/10.3322/caac.v68.6 http://doi.wiley.com/10.3322/caac.v68.6

YANG Y M , HONG P , XU W W , et al . Advances in targeted therapy for esophageal cancer [J ] . Signal Transduct Target Ther , 2020 , 5 ( 1 ): 229 . DOI: 10.1038/s41392-020-00323-3 http://doi.org/10.1038/s41392-020-00323-3 https://doi.org/10.1038/s41392-020-00323-3 https://doi.org/10.1038/s41392-020-00323-3

ARNOLD M , SOERJOMATARAM I , FERLAY J , et al . Global incidence of oesophageal cancer by histological subtype in 2012 [J ] . Gut , 2015 , 64 ( 3 ): 381 - 387 . DOI: 10.1136/gutjnl-2014-308124 http://doi.org/10.1136/gutjnl-2014-308124 https://gut.bmj.com/lookup/doi/10.1136/gutjnl-2014-308124 https://gut.bmj.com/lookup/doi/10.1136/gutjnl-2014-308124

CHUNG C S , LEE Y C , WU M S . Prevention strategies for esophageal cancer: perspectives of the east vs west [J ] . Best Pract Res Clin Gastroenterol , 2015 , 29 ( 6 ): 869 - 883 . DOI: 10.1016/j.bpg.2015.09.010 http://doi.org/10.1016/j.bpg.2015.09.010 https://linkinghub.elsevier.com/retrieve/pii/S1521691815001237 https://linkinghub.elsevier.com/retrieve/pii/S1521691815001237

NOONE A M , CRONIN K A , ALTEKRUSE S F , et al . Cancer incidence and survival trends by subtype using data from the surveillance epidemiology and end results program, 1992-2013 [J ] . Cancer Epidemiol Biomarkers Prev , 2017 , 26 ( 4 ): 632 - 641 . DOI: 10.1158/1055-9965.EPI-16-0520 http://doi.org/10.1158/1055-9965.EPI-16-0520 http://cebp.aacrjournals.org/lookup/doi/10.1158/1055-9965.EPI-16-0520 http://cebp.aacrjournals.org/lookup/doi/10.1158/1055-9965.EPI-16-0520

YANG X P , COULOMBE-HUNTINGTON J , KANG S L , et al . Widespread expansion of protein interaction capabilities by alternative splicing [J ] . Cell , 2016 , 164 ( 4 ): 805 - 817 . DOI: 10.1016/j.cell.2016.01.029 http://doi.org/10.1016/j.cell.2016.01.029 https://linkinghub.elsevier.com/retrieve/pii/S0092867416300435 https://linkinghub.elsevier.com/retrieve/pii/S0092867416300435

PELLARIN I , DALL'ACQUA A , GAMBELLI A , et al . Splicing factor proline- and glutamine-rich (SFPQ) protein regulates platinum response in ovarian cancer-modulating SRSF2 activity [J ] . Oncogene , 2020 , 39 ( 22 ): 4390 - 4403 . DOI: 10.1038/s41388-020-1292-6 http://doi.org/10.1038/s41388-020-1292-6 https://doi.org/10.1038/s41388-020-1292-6 https://doi.org/10.1038/s41388-020-1292-6

ANANDE G , DESHPANDE N P , MARESCHAL S , et al . RNA splicing alterations induce a cellular stress response associated with poor prognosis in acute myeloid leukemia [J ] . Clin Cancer Res , 2020 , 26 ( 14 ): 3597 - 3607 . DOI: 10.1158/1078-0432.CCR-20-0184 http://doi.org/10.1158/1078-0432.CCR-20-0184 http://clincancerres.aacrjournals.org/lookup/doi/10.1158/1078-0432.CCR-20-0184 http://clincancerres.aacrjournals.org/lookup/doi/10.1158/1078-0432.CCR-20-0184

SANFORD J R , WANG X , MORT M , et al . Splicing factor SFRS1 recognizes a functionally diverse landscape of RNA transcripts [J ] . Genome Res , 2009 , 19 ( 3 ): 381 - 394 . DOI: 10.1101/gr.082503.108 http://doi.org/10.1101/gr.082503.108 http://genome.cshlp.org/lookup/doi/10.1101/gr.082503.108 http://genome.cshlp.org/lookup/doi/10.1101/gr.082503.108

ZHOU X X , WANG R , LI X B , et al . Splicing factor SRSF1 promotes gliomagenesis via oncogenic splice-switching of MYO1B [J ] . J Clin Invest , 2019 , 129 ( 2 ): 676 - 693 . DOI: 10.1172/JCI120279 http://doi.org/10.1172/JCI120279 https://www.jci.org/articles/view/120279 https://www.jci.org/articles/view/120279

HUANG J , XU J M , CHEN Y , et al . Camrelizumab versus investigator's choice of chemotherapy as second-line therapy for advanced or metastatic oesophageal squamous cell carcinoma (ESCORT): a multicentre, randomised, open-label, phase 3 study [J ] . Lancet Oncol , 2020 , 21 ( 6 ): 832 - 842 . DOI: 10.1016/S1470-2045(20)30110-8 http://doi.org/10.1016/S1470-2045(20)30110-8 https://linkinghub.elsevier.com/retrieve/pii/S1470204520301108 https://linkinghub.elsevier.com/retrieve/pii/S1470204520301108

LUO H Y , LU J , BAI Y X , et al . Effect of camrelizumab vs placebo added to chemotherapy on survival and progression-free survival in patients with advanced or metastatic esophageal squamous cell carcinoma: the ESCORT-1st randomized clinical trial [J ] . JAMA , 2021 , 326 ( 10 ): 916 - 925 . DOI: 10.1001/jama.2021.12836 http://doi.org/10.1001/jama.2021.12836 https://jamanetwork.com/journals/jama/fullarticle/2784143 https://jamanetwork.com/journals/jama/fullarticle/2784143

CARTEGNI L , CHEW S L , KRAINER A R . Listening to silence and understanding nonsense: exonic mutations that affect splicing [J ] . Nat Rev Genet , 2002 , 3 ( 4 ): 285 - 298 . DOI: 10.1038/nrg775 http://doi.org/10.1038/nrg775 https://doi.org/10.1038/nrg775 https://doi.org/10.1038/nrg775

WU H , SUN S Y , TU K , et al . A splicing-independent function of SF2/ASF in microRNA processing [J ] . Mol Cell , 2010 , 38 ( 1 ): 67 - 77 . DOI: 10.1016/j.molcel.2010.02.021 http://doi.org/10.1016/j.molcel.2010.02.021 https://linkinghub.elsevier.com/retrieve/pii/S1097276510001735 https://linkinghub.elsevier.com/retrieve/pii/S1097276510001735

MARTÍNEZ-TERROBA E , EZPONDA T , BÉRTOLO C , et al . The oncogenic RNA-binding protein SRSF1 regulates LIG1 in non-small cell lung cancer [J ] . Lab Invest , 2018 , 98 ( 12 ): 1562 - 1574 . DOI: 10.1038/s41374-018-0128-2 http://doi.org/10.1038/s41374-018-0128-2 https://doi.org/10.1038/s41374-018-0128-2 https://doi.org/10.1038/s41374-018-0128-2

DUAN Y Q , JIA Y L , WANG J L , et al . Long noncoding RNA DGCR5 involves in tumorigenesis of esophageal squamous cell carcinoma via SRSF1-mediated alternative splicing of Mcl-1 [J ] . Cell Death Dis , 2021 , 12 ( 6 ): 587 . DOI: 10.1038/s41419-021-03858-7 http://doi.org/10.1038/s41419-021-03858-7 https://doi.org/10.1038/s41419-021-03858-7 https://doi.org/10.1038/s41419-021-03858-7

PASCHALIS A , SHARP A , WELTI J C , et al . Alternative splicing in prostate cancer [J ] . Nat Rev Clin Oncol , 2018 , 15 ( 11 ): 663 - 675 . DOI: 10.1038/s41571-018-0085-0 http://doi.org/10.1038/s41571-018-0085-0 https://doi.org/10.1038/s41571-018-0085-0 https://doi.org/10.1038/s41571-018-0085-0

BIEGING-ROLETT K T , KAISER A M , MORGENS D W , et al . Zmat3 is a key splicing regulator in the p53 tumor suppression program [J ] . Mol Cell , 2020 , 80(3): 452-469. e9.

CHEN L L , LUO C L , SHEN L , et al . SRSF1 prevents DNA damage and promotes tumorigenesis through regulation of DBF4B pre-mRNA splicing [J ] . Cell Rep , 2017 , 21 ( 12 ): 3406 - 3413 . DOI: 10.1016/j.celrep.2017.11.091 http://doi.org/10.1016/j.celrep.2017.11.091 https://linkinghub.elsevier.com/retrieve/pii/S2211124717317588 https://linkinghub.elsevier.com/retrieve/pii/S2211124717317588

WANG J L , LIU T X , WANG M J , et al . SRSF1-dependent alternative splicing attenuates BIN1 expression in non-small cell lung cancer [J ] . J Cell Biochem , 2020 , 121 ( 2 ): 946 - 953 . DOI: 10.1002/jcb.v121.2 http://doi.org/10.1002/jcb.v121.2 https://onlinelibrary.wiley.com/toc/10974644/121/2 https://onlinelibrary.wiley.com/toc/10974644/121/2

BARBAGALLO D , CAPONNETTO A , BREX D , et al . CircSMARCA5 regulates VEGFA mRNA splicing and angiogenesis in glioblastoma multiforme through the binding of SRSF1 [J ] . Cancers (Basel) , 2019 , 11 ( 2 ): E194 .

ZHANG X T , ZOU G Y , LI X Y , et al . An isoflavone derivative potently inhibits the angiogenesis and progression of triple-negative breast cancer by targeting the MTA2/SerRS/VEGFA pathway [J ] . Cancer Biol Med , 2020 , 17 ( 3 ): 693 - 706 . DOI: 10.20892/j.issn.2095-3941.2020.0010 http://doi.org/10.20892/j.issn.2095-3941.2020.0010 http://www.cancerbiomed.org/index.php/cocr/article/view/1675 http://www.cancerbiomed.org/index.php/cocr/article/view/1675

LU J , WANG Y H , YOON C , et al . Circular RNA circ-RanGAP1 regulates VEGFA expression by targeting miR-877-3p to facilitate gastric cancer invasion and metastasis [J ] . Cancer Lett , 2020 , 471 : 38 - 48 . DOI: 10.1016/j.canlet.2019.11.038 http://doi.org/10.1016/j.canlet.2019.11.038 https://linkinghub.elsevier.com/retrieve/pii/S0304383519306020 https://linkinghub.elsevier.com/retrieve/pii/S0304383519306020

HAMDOLLAH ZADEH M A , AMIN E M , HOAREAU-AVEILLA C , et al . Alternative splicing of TIA-1 in human colon cancer regulates VEGF isoform expression, angiogenesis, tumour growth and bevacizumab resistance [J ] . Mol Oncol , 2015 , 9 ( 1 ): 167 - 178 . DOI: 10.1016/j.molonc.2014.07.017 http://doi.org/10.1016/j.molonc.2014.07.017 http://doi.wiley.com/10.1016/j.molonc.2014.07.017 http://doi.wiley.com/10.1016/j.molonc.2014.07.017

ABNET C C , ARNOLD M , WEI W Q . Epidemiology of esophageal squamous cell carcinoma [J ] . Gastroenterology , 2018 , 154 ( 2 ): 360 - 373 . DOI: 10.1053/j.gastro.2017.08.023 http://doi.org/10.1053/j.gastro.2017.08.023 https://linkinghub.elsevier.com/retrieve/pii/S0016508517360390 https://linkinghub.elsevier.com/retrieve/pii/S0016508517360390

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