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Current Molecular Medicine

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ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

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Research Article

Sema3A Alleviates the Malignant Behaviors of Gastric Cancer Cells by Inhibiting NRP-1

Author(s): Hongqiong Yang, Yaojun Zhou*, Liangzhi Wang, Mengjia Lv, Jinling Sun, Zhenguo Luo and Junbo He

Volume 24, Issue 7, 2024

Published on: 21 September, 2023

Page: [931 - 939] Pages: 9

DOI: 10.2174/1566524023666230801124826

Price: $65

Abstract

Aims and objectives: Semaphorin3A (Sema3a) is lowly expressed in the peripheral blood of gastric cancer patients, suggesting Sema3a may be involved in the progression of gastric cancer. Nevertheless, the specific role and the potential regulatory mechanism of Sema3a in gastric cancer is still obscure. Neuropilin-1 (NRP-1) has been reported to interact with Sema3a; herein, we intended to reveal the role and regulatory mechanism of Sema3a/neuropilin-1 (NRP-1) in gastric cancer progression.

Methods: Cell transfection was carried out to regulate gene expression. CCK-8 and colony formation assays were applied to estimate cell proliferation. Scratch assay and transwell assay were conducted to assess the cell migration and invasion abilities. Angiogenesis ability was assessed using a tubule-forming assay. The expression of corresponding genes and proteins were detected by RT-qPCR and western blot, respectively.

Results: Data showed that Sema3a was downregulated in gastric cancer cells and NRP-1 was upregulated. Sema3a overexpression repressed NRP-1 level in AGS cells. Overexpression of Sema3a inhibited cell proliferation, migration, and invasion abilities as well as epithelial-mesenchymal transition (EMT) of AGS cells. Overexpression of Sema3a inhibited tube formation and reduced the expression of VEGFA/VEGFR2 in AGS cells. However, the effects of Sema3a overexpression on the malignant behaviors in AGS cells were partly reversed by NRP-1 overexpression. Additionally, Sema3a overexpression enhanced the inhibitory effects of Ramucirumab, an anti-VEGFR2 agent, on the proliferative, migratory, and invasive capabilities as well as EMT in AGS cells.

Conclusion: In conclusion, Sema3a alleviates the proliferation, migration, invasion, and angiogenesis capabilities of gastric cancer cells via repressing NRP-1. This finding may provide potential targets for gastric cancer therapy.

« Previous Next »
[1]
Lim B, Kim HJ, Heo H, et al. Epigenetic silencing of miR-1271 enhances MEK1 and TEAD4 expression in gastric cancer. Cancer Med 2018; 7(7): 3411-24.
[http://dx.doi.org/10.1002/cam4.1605] [PMID: 29862663]
[2]
Hu ML, Xiong SW, Zhu SX, Xue XX, Zhou XD. MicroRNAs in gastric cancer: From bench to bedside. Neoplasma 2019; 66(2): 176-86.
[http://dx.doi.org/10.4149/neo_2018_180703N439] [PMID: 30509106]
[3]
Zhao B, Zhang J, Zhang J, et al. Risk factors associated with lymph node metastasis for early gastric cancer patients who underwent non-curative endoscopic resection: A systematic review and meta-analysis. J Gastrointest Surg 2019; 23(7): 1318-28.
[http://dx.doi.org/10.1007/s11605-018-3924-5] [PMID: 30187319]
[4]
Fang X, Pan H, Leng R, Ye D. Long noncoding RNAs: Novel insights into gastric cancer. Cancer Lett 2015; 356(2): 357-66.
[http://dx.doi.org/10.1016/j.canlet.2014.11.005] [PMID: 25444905]
[5]
Sun Q, Li Y. The inhibitory effect of pseudolaric acid B on gastric cancer and multidrug resistance via Cox-2/PKC-α/P-gp pathway. PLoS One 2014; 9(9): e107830.
[http://dx.doi.org/10.1371/journal.pone.0107830] [PMID: 25250794]
[6]
Li Y, Zhang M, Dorfman RG, et al. SIRT2 promotes the migration and invasion of gastric cancer through ras/erk/jnk/mmp-9 pathway by increasing pepck1-related metabolism. Neoplasia 2018; 20(7): 745-56.
[http://dx.doi.org/10.1016/j.neo.2018.03.008] [PMID: 29925042]
[7]
Tian T, Zhang L, Tang K, et al. SEMA3A exon 9 expression is a potential prognostic marker of unfavorable recurrence-free survival in patients with tongue squamous cell carcinoma. DNA Cell Biol 2020; 39(4): 555-62.
[http://dx.doi.org/10.1089/dna.2019.5109] [PMID: 32074456]
[8]
Narematsu M, Kamimura T, Yamagishi T, Nakajima Y. Hypoxia-induced downregulation of Sema3a and CXCL12/CXCR4 regulate the formation of the coronary artery stem at the proper site. J Mol Cell Cardiol 2020; 147: 62-73.
[http://dx.doi.org/10.1016/j.yjmcc.2020.08.001] [PMID: 32777295]
[9]
Bica C, Tirpe A, Nutu A, et al. Emerging roles and mechanisms of semaphorins activity in cancer. Life Sci 2023; 318: 121499.
[http://dx.doi.org/10.1016/j.lfs.2023.121499] [PMID: 36775114]
[10]
Lucarini G, Simonetti O, Lazzarini R, Giantomassi F, Goteri G, Offidani A. Vascular endothelial growth factor/semaphorin-3A ratio and SEMA3A expression in cutaneous malignant melanoma. Melanoma Res 2020; 30(5): 433-42.
[http://dx.doi.org/10.1097/CMR.0000000000000674] [PMID: 32516239]
[11]
Liu F, Wang C, Huang H, et al. SEMA3A-mediated crosstalk between prostate cancer cells and tumor-associated macrophages promotes androgen deprivation therapy resistance. Cell Mol Immunol 2021; 18(3): 752-4.
[http://dx.doi.org/10.1038/s41423-021-00637-4] [PMID: 33558684]
[12]
Zhang X, He Q, Sun L, et al. Comparing microrna profilings of purified her-2-negative and her-2-positive cells validates mir-362-5p/sema3a as characteristic molecular change in triple-negative breast cancers. Dis Markers 2019; 2019: 1-12.
[http://dx.doi.org/10.1155/2019/6057280] [PMID: 31929841]
[13]
Tang C, Gao X, Liu H, Jiang T, Zhai X. Decreased expression of sema3a is associated with poor prognosis in gastric carcinoma. Int J Clin Exp Pathol 2014; 7(8): 4782-94.
[PMID: 25197349]
[14]
Chaudhary B, Khaled YS, Ammori BJ, Elkord E. Neuropilin 1: Function and therapeutic potential in cancer. Cancer Immunol Immunother 2014; 63(2): 81-99.
[http://dx.doi.org/10.1007/s00262-013-1500-0] [PMID: 24263240]
[15]
Cao C, Yin C, Shou S, et al. Ulinastatin protects against lps-induced acute lung injury by attenuating tlr4/nf-κb pathway activation and reducing inflammatory mediators. Shock 2018; 50(5): 595-605.
[http://dx.doi.org/10.1097/SHK.0000000000001104] [PMID: 29324628]
[16]
Zhuo YJ, Shi Y, Wu T. NRP 1 and KDR polymorphisms are associated with survival time in patients with advanced gastric cancer. Oncol Lett 2019; 18(5): 4629-38.
[http://dx.doi.org/10.3892/ol.2019.10842] [PMID: 31611971]
[17]
Refolo MG, Lotesoriere C, Lolli IR, Messa C, D’Alessandro R. Molecular mechanisms of synergistic action of ramucirumab and paclitaxel in gastric cancers cell lines. Sci Rep 2020; 10(1): 7162.
[http://dx.doi.org/10.1038/s41598-020-64195-x] [PMID: 32346056]
[18]
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative pcr and the 2(-delta delta c(t)) method. Methods 2001; 25(4): 402-8.
[http://dx.doi.org/10.1006/meth.2001.1262] [PMID: 11846609]
[19]
Zhang Q, Lu S, Li T, et al. ACE2 inhibits breast cancer angiogenesis via suppressing the VEGFa/VEGFR2/ERK pathway. J Exp Clin Cancer Res 2019; 38(1): 173.
[http://dx.doi.org/10.1186/s13046-019-1156-5] [PMID: 31023337]
[20]
Iragavarapu-Charyulu V, Wojcikiewicz E, Urdaneta A. Semaphorins in angiogenesis and autoimmune diseases: Therapeutic targets? Front Immunol 2020; 11: 346.
[http://dx.doi.org/10.3389/fimmu.2020.00346] [PMID: 32210960]
[21]
Fard D, Tamagnone L. Semaphorins in health and disease. Cytokine Growth Factor Rev 2021; 57: 55-63.
[http://dx.doi.org/10.1016/j.cytogfr.2020.05.006] [PMID: 32900601]
[22]
Li J, Wang T, Li C, Wang Z, Wang P, Zheng L. Sema3A and HIF1α co‐overexpressed iPSC-MSCs/HA scaffold facilitates the repair of calvarial defect in a mouse model. J Cell Physiol 2020; 235(10): 6754-66.
[http://dx.doi.org/10.1002/jcp.29569] [PMID: 32012286]
[23]
Kawasaki T, Bekku Y, Suto F, et al. Requirement of neuropilin 1-mediated Sema3A signals in patterning of the sympathetic nervous system. Development 2002; 129(3): 671-80.
[http://dx.doi.org/10.1242/dev.129.3.671] [PMID: 11830568]
[24]
Vilbig R, Cosmano J, Giger R, Rochlin MW. Distinct roles for Sema3A, Sema3F, and an unidentified trophic factor in controlling the advance of geniculate axons to gustatory lingual epithelium. J Neurocytol 2004; 33(6): 591-606.
[http://dx.doi.org/10.1007/s11068-005-3329-8] [PMID: 16217616]
[25]
Rezaeepoor M, Shapoori S, Ganjalikhani-hakemi M, et al. Decreased expression of sema3a, an immune modulator, in blood sample of multiple sclerosis patients. Gene 2017; 610: 59-63.
[http://dx.doi.org/10.1016/j.gene.2017.02.013] [PMID: 28188869]
[26]
Yang ZG, Wen RT, Qi K, et al. The neuropilin-1 ligand, sema3a, acts as a tumor suppressor in the pathogenesis of acute leukemia. Anat Rec 2019; 302(7): 1127-35.
[http://dx.doi.org/10.1002/ar.24016] [PMID: 30378769]
[27]
Muche A, Bigl M, Arendt T, Schliebs R. Expression of vascular endothelial growth factor (vegf) mrna, vegf receptor 2 (flk-1) mrna, and of vegf co‐receptor neuropilin (nrp)-1 mrna in brain tissue of aging tg2576 mice by in situ hybridization. Int J Dev Neurosci 2015; 43(1): 25-34.
[http://dx.doi.org/10.1016/j.ijdevneu.2015.03.003] [PMID: 25797338]
[28]
Straume O, Akslen LA. Increased expression of VEGF-receptors (FLT-1, KDR, NRP-1) and thrombospondin-1 is associated with glomeruloid microvascular proliferation, an aggressive angiogenic phenotype, in malignant melanoma. Angiogenesis 2003; 6(4): 295-301.
[http://dx.doi.org/10.1023/B:AGEN.0000029408.08638.aa] [PMID: 15166498]
[29]
Hu C, Jiang X. Role of nrp-1 in vegf-vegfr2-independent tumorigenesis. Target Oncol 2016; 11(4): 501-5.
[http://dx.doi.org/10.1007/s11523-016-0422-0] [PMID: 26916409]
[30]
Karami E, Naderi S, Roshan R, Behdani M, Kazemi-Lomedasht F. Targeted therapy of angiogenesis using anti-vegfr2 and anti-nrp-1 nanobodies. Cancer Chemother Pharmacol 2022; 89(2): 165-72.
[http://dx.doi.org/10.1007/s00280-021-04372-5] [PMID: 34988654]

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