Effects of SERPINE1 on proliferation, migration, invasion and apoptosis of colon cancer cells

Dehe CHEN; Dengyu LI; Gang GUO; Jie WANG; Qian ZHOU; Hongtao LI

doi:10.16016/j.2097-0927.202311079

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Effects of SERPINE1 on proliferation, migration, invasion and apoptosis of colon cancer cells

Basic Medicine | 更新时间：2026-01-09

- Effects of SERPINE1 on proliferation, migration, invasion and apoptosis of colon cancer cells
- Journal of Army Medical University Vol. 46, Issue 15, Pages: 1751-1762(2024)
- 作者机构：
  
  1.750000 银川，宁夏医科大学临床医学院胃肠外科
  2.476000 河南商丘，商丘市第五人民医院普外科
  3.730000 兰州，联勤保障部队第九四〇医院普外科
  4.730000 兰州，甘肃省干细胞与基因药物重点实验室
- 作者简介：
- 基金信息：
  
  the Natural Science Foundation of Gansu Province(22JR5RA005)
- DOI：10.16016/j.2097-0927.202311079
  CLC： R341;R730.23;R735.35
- Received：16 November 2023，
  
  Revised：2023-12-23，
  
  Published：15 August 2024
- 稿件说明：
移动端阅览
Dehe CHEN, Dengyu LI, Gang GUO, et al. Effects of SERPINE1 on proliferation, migration, invasion and apoptosis of colon cancer cells[J]. Journal of Army Medical University, 2024, 46(15): 1751-1762.
DOI：

Dehe CHEN, Dengyu LI, Gang GUO, et al. Effects of SERPINE1 on proliferation, migration, invasion and apoptosis of colon cancer cells[J]. Journal of Army Medical University, 2024, 46(15): 1751-1762. DOI： 10.16016/j.2097-0927.202311079.

摘要

目的

探究丝氨酸蛋白酶抑制剂1(serine proteinase inhibitor family E member 1，SERPINE1)在结肠癌中的表达及对结肠癌细胞恶性生物学行为的影响。

方法

通过starBase和TISIDB数据库分析471个结肠癌及41个正常结肠组织中SERPINE1的表达及其与临床分期、预后生存的关系；收集联勤保障部队第九四〇医院5例结肠癌患者癌组织与对应的癌旁组织标本，应用RT-qPCR和Western blot验证SERPINE1在结肠癌中的表达。构建SERPINE1过表达与干扰表达的慢病毒载体，进行结肠癌RKO和LoVo细胞株转染，通过RT-qPCR和Western blot评估SERPINE1过表达和干扰表达的效果，通过细胞计数试剂盒(cell counting kit-8，CCK-8)、克隆形成实验、Transwell实验和Hoechst凋亡细胞核染色评估细胞的增殖、迁移与侵袭能力和细胞的凋亡情况；应用Western blot检测SERPINE1对磷脂酰激酶3(phosphatidyl-inositol 3-kinase，PI3K)/蛋白激酶B(protein kinase B，AKT)信号通路的影响。

结果

数据库分析发现SERPINE1在结肠癌中高表达，且与患者的肿瘤临床分期正相关，与预后总生存期负相关(

0.05)。转染过表达的慢病毒载体后细胞的增殖、迁移与侵袭能力增强，而细胞的凋亡减弱；反之，在转染干扰表达的慢病毒载体后细胞的增殖、迁移与侵袭能力减弱，而细胞的凋亡增强(

0.05)。通过Western blot实验发现转染SERPINE1过表达的慢病毒载体后细胞PI3K和AKT表达无明显变化，而磷酸化PI3K(p-PI3K)和磷酸化AKT(p-AKT)表达增加，反之转染SERPINE1干扰表达的慢病毒载体细胞PI3K和AKT表达无明显变化，而p-PI3K和p-AKT表达减少，灰度值定量分析p-PI3K/PI3K和p-AKT/AKT比值差异有统计学意义(

0.05)。

结论

SERPINE1在结肠癌中高表达，与患者临床分期及预后相关；SERPINE1过表达可能通过激活PI3K/AKT信号通路促进结肠癌细胞的增殖、迁移与侵袭，抑制其凋亡。

Abstract

Objective

To explore the expression of serine proteinase inhibitor family E member 1 (SERPINE1) in colon cancer and its effect on the malignant biological behaviors of colon cancer cells.

Methods

starBase and TISIDB databases were used to analyze the expression of SERPINE1 in 471 patients with colon cancer and 41 paracancerous tissues

and the relationships of its differential expression with clinical stage and prognostic survival were analyzed. The cancer specimens and paracancerous tissues from 5 patients with colon cancer were collected in No. 940 Hospital of Joint Logistic Support Force

and RT-qPCR and Western blotting were employed to detect the expression of SERPINE1 at mRNA and protein levels. After lentiviral vectors of SERPINE1 overexpression and interference were constructed and transfected into colon cancer RKO and LoVo cells. The experimental cells were assessed by RT-qPCR and Western blotting to verify the efficiency of overexpression and interference. Then cell proliferation

migration

invasion and apoptosis were evaluated by CCK-8 assay

clone formation test

Transwell test and Hoechst apoptotic nuclear staining

respectviely. Finally

Western blotting was applied to determine the effect of SERPINE1 on phosphatidyl-inositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway.

Results

Database analysis showed that SERPINE1 was highly expressed

positively correlated with the clinical stage and negatively correlated with the overall survival in colon cancer patients (

0.05). Transfection of overexpression lentiviral vector resulted in enhanced cell proliferation

invasion and migration abilities while weakened apoptosis in RKO and LoVo cells. On the contrary

SERPINE1 interference reduced the abilities of cell proliferation

invasion and migration but improved cell apoptosis (

0.05). Western blotting showed that overexpression of SERPINE1 had no effect on the expression of PI3K and AKT

but increased the expression of p-PI3K and p-AKT

and SERPINE1 interference also had no change in PI3K and AKT expression and reduced the levels of their phosphorylation levels. Statistical differences were observed in relative quantitative analysis on the ratios of p-PI3K/PI3K and p-AKT/AKT (

0.05).

Conclusion

SERPINE1 is highly expressed

and correlated with clinical stage and prognosis of patients with colon cancer. Its overexpression promotes the proliferation

migration

invasion and inhibits apoptosis of colon cancer RKO and LoVo cells through PI3K/AKT signaling pathway.

关键词

Keywords

references

BRAY F, LAVERSANNE M, WEIDERPASS E, et al . The ever-increasing importance of cancer as a leading cause of premature death worldwide[J ] . Cancer, 2021, 127(16): 3029-3030. DOI: 10.1002/cncr.33587.

SUNG H, FERLAY J, SIEGEL R L, et al . Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J ] . CA Cancer J Clin, 2021, 71(3): 209-249. DOI: 10.3322/caac.21660.

ZHENG R S, ZHANG S W, ZENG H M, et al . Cancer incidence and mortality in China, 2016[J ] . J Natl Cancer Cent, 2022, 2(1): 1-9. DOI: 10.1016/j.jncc.2022.02.002.

KUIPERS E J, GRADY W M, LIEBERMAN D, et al . Colorectal cancer[J ] . Nat Rev Dis Primers, 2015, 1: 15065. DOI: 10.1038/nrdp.2015.65.

ZHANG F, ZHANG Y Y, ZHAO W W, et al . Metabolomics for biomarker discovery in the diagnosis, prognosis, survival and recurrence of colorectal cancer: a systematic review[J ] . Oncotarget, 2017, 8(21): 35460-35472. DOI: 10.18632/oncotarget.16727.

郭天安, 谢丽, 赵江, 等. 中国结直肠癌1988-2009年发病率和死亡率趋势分析[J]. 中华胃肠外科杂志, 2018, 21 (1): 33-40. DOI: 10.3706/cma.j.issn.1671-0274.2018.01.007.

GUO T A, XIE L, ZHAO J, et al . Trend analysis of morbidity and mortality o f colorectal cancer in China from 1988 to 2009[J ] . Chin J Gastrointest Surg, 2018, 21 (1): 33-40. DOI: 10.3706/cma.j.issn.1671-0274.2018.01.007.

MORROW G B, MUTCH N J. Past, present, and future perspectives of plasminogen activator inhibitor 1 (PAI-1)[J]. Semin Thromb Hemost, 2023, 49(3): 305-313. DOI: 10.1055/s-0042-1758791.

陈德合, 郭刚, 王杰, 等. SERPINE1在肿瘤中功能及应用的研究进展[J]. 联勤军事医学, 2023, 37 (9): 813-816, 封3. DOI: 10.13730/j.issn.2097-2148.2023.09.019.

CHEN D H, GUO G, WANG J, et al . Research progress on the function and application of SERPINE1 in tumors[J ] . Mil Med Jnt Log, 2023, 37 (9): 813-816, Cover 3. DOI: 10.13730/j.issn.2097-2148.2023.09.019.

WANG B F, GU B H, ZHANG T, et al . Good or bad: paradox of plasminogen activator inhibitor 1 (PAI-1) in digestive system tumors[J ] . Cancer Lett, 2023, 559: 216117. DOI: 10.1016/j.canlet.2023.216117.

WANG D, YANG L Y, LIU Z, et al . PAI-1 overexpression promotes invasion and migration of esophageal squamous carcinoma cells[J ] . Hereditas, 2020, 42(3): 287-295. DOI: 10.16288/j.yczz.19-334.

OHUCHI K, AMAGAI R, IKAWA T, et al . Plasminogen activating inhibitor-1 promotes angiogenesis in cutaneous angiosarcomas[J ] . Exp Dermatol, 2023, 32(1): 50-59. DOI: 10.1111/exd.14681.

LI Y Q, SHEN L, TAO K L, et al . Key roles of p53 signaling pathway-related factors GADD45Band SERPINE1 in the occurrence and development of gastric cancer[J ] . Mediators Inflamm, 2023, 2023: 6368893. DOI: 10.1155/2023/6368893.

WANG W J, LI H T, YU J P, et al . A competing endogenous RNA network reveals novel potential lncRNA, miRNA, and mRNA biomarkers in the prognosis of human colon adenocarcinoma[J ] . J Surg Res, 2019, 235: 22-33. DOI: 10.1016/j.jss.2018.09.053.

LIU Y, LI C, DONG L J, et al . Identification and verification of three key genes associated with survival and prognosis of COAD patients via integrated bioinformatics analysis[J ] . Biosci Rep, 2020, 40(9): BSR20200141. DOI: 10.1042/BSR20200141..

WANG Y G, WANG J Y, GAO J C, et al . The expression of SERPINE1 in colon cancer and its regulatory network and prognostic value[J ] . BMC Gastroenterol, 2023, 23(1): 33. DOI: 10.1186/s12876-022-02625-y.

MIAO Z H, LIU S Y, XIAO X W, et al . LINC00342 regulates cell proliferation, apoptosis, migration and invasion in colon adenocarcinoma via miR-545-5p/MDM2 axis[J ] . Ge ne, 2020, 743: 144604. DOI: 10.1016/j.gene.2020.144604..

BILLER L H, SCHRAG D. Diagnosis and treatment of metastatic colorectal cancer: a review[J]. JAMA, 2021, 325(7): 669-685. DOI: 10.1001/jama.2021.0106.

LI N, LU B, LUO C Y, et al . Incidence, mortality, survival, risk factor and screening of colorectal cancer: a comparison among China, Europe, and northern America[J ] . Cancer Lett, 2021, 522: 255-268. DOI: 10.1016/j.canlet.2021.09.034.

PATEL S G, KARLITZ J J, YEN T, et al . The rising tide of early-onset colorectal cancer: a comprehensive review of epidemiology, clinical features, biology, risk factors, prevention, and early detection[J ] . Lancet Gastroenterol Hepatol, 2022, 7(3): 262-274. DOI: 10.1016/S2468-1253(21)00426-X.

SINICROPE F A. Increasing incidence of early-onset colorectal cancer[J]. N Engl J Med, 2022, 386(16): 1547-1558. DOI: 10.1056/nejmra2200869.

XUE W, SUN C Y, YUAN H, et al . Establishment and analysis of an individualized EMT-related gene signature for the prognosis of breast cancer in female patients[J ] . Dis Markers, 2022, 2022: 1289445. DOI: 10.1155/2022/1289445.

WU P, ZHANG Z H, YUAN Y L, et al . A tumor immune microenvironment-related integrated signature can predict the pathological response and prognosis of esophageal squamous cell carcinoma following neoadjuvant chemoradiotherapy: a multicenter study in China[J ] . Int J Surg, 2022, 107: 106960. DOI: 10.1016/j.ijsu.2022.106960.

WANG Y C, ZHANG L P, SHI G H, et al . Effects of inflammatory response genes on the immune microenvironment in colorectal cancer[J ] . Front Genet, 2022, 13: 886949. DOI: 10.3389/fgene.2022.886949.

SU Y H, WU Y Z, ANN D K, et al . Obesity promotes radioresistance through SERPINE1-mediated aggressiveness and DNA repair of triple-negative breast cancer[J ] . Cell Death Dis, 2023, 14(1): 53. DOI: 10.1038/s41419-023-05576-8.

LI X, WANG C X, ZHANG H, et al . circFNDC3B accelerates vasculature formation and metastasis in oral squamous cell carcinoma[J ] . Cancer Res, 2023, 83(9): 1459-1475. DOI: 10.1158/0008-5472.CAN-22-2585.

MAO Y S, LI W F, HUA B, et al . Silencing of ELK3 induces S-M phase arrest and apoptosis and upregulates SERPINE1 expression reducing migration in prostate cancer cells[J ] . Biomed Res Int, 2020, 2020: 2406159. DOI: 10.1155/2020/2406159.

TENG F, ZHANG J X, CHEN Y, et al . LncRNA NKX2-1-AS1 promotes tumor progression and angiogenesis via upregulation of SERPINE1 expression and activation of the VEGFR-2 signaling pathway in gastric cancer[J ] . Mol Oncol, 2021, 15(4): 1234-1255. DOI: 10.1002/1878-0261.12911..

ZHANG Q, LEI L, JING D. Knockdown of SERPINE1 reverses resistance of triple-negative breast cancer to paclitaxel via suppression of VEGFA[J ] . Oncol Rep, 2020, 44(5): 1875-1884. DOI: 10.3892/or.2020.7770.

CHAVES-MOREIRA D, MITCHELL M A, ARRUZA C, et al . The transcription factor PAX8 promotes angiogenesis in ovarian cancer through interaction with SOX17[J ] . Sci Signal, 2022, 15(728): eabm2496. DOI: 10.1126/scisignal.abm2496.

LI X, WU P, TANG Y Y, et al . Down-regulation of MiR-181c-5p promotes epithelial-to-mesenchymal transition in laryngeal squamous cell carcinoma via targeting SERPINE1 [J ] . Front Oncol, 2020, 10: 544476. DOI: 10.3389/fonc.2020.544476..

ZENG C Y, CHEN Y X. HTR1D, TIMP1, SERPINE1, MMP3 and CNR2 affect the survival of patients with colon adenocarcinoma[J]. Oncol Lett, 2019, 18(3): 2448-2454. DOI: 10.3892/ol.2019.10545.

HU B W, CHEN Z W, WANG X G, et al . MicroRNA-148a-3p directly targets SERPINE1 to suppress EMT-mediated colon adenocarcinoma progression[J ] . Cancer Manag Res, 2021, 13: 6349-6362. DOI: 10.2147/CMAR.S302777.

KIM W T, MUN J Y, BAEK S W, et al . Secretory SERPINE1 expression is increased by antiplatelet therapy, inducing MMP1 expression and increasing colon cancer metastasis[J ] . Int J Mol Sci, 2022, 23(17): 9596. DOI: 10.3390/ijms23179596.

ZHANG W W, YANG S F, CHEN D T, et al . SOX2-OT induced by PAI-1 promotes triple-negative breast cancer cells metastasis by sponging miR-942-5p and activating PI3K/Akt signaling[J ] . Cell Mol Life Sci, 2022, 79(1): 59. DOI: 10.1007/s00018-021-04120-1.

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