SNORD3A acts as a potential prognostic and therapeutic biomarker in gastric cancer

Graphical abstract

SNORD3A acts as a potential prognostic and therapeutic biomarker in gastric cancer
PDF
HTML

Keywords

Gastric cancer
Gastric cancer invasiveness
Gastric cancer migration
Gastric cancer proliferation
GO-KEGG analysis
Kaplan-Meier curves
Prognostic biomarker
SNORD3A
Therapeutic biomarker

Categories

How to Cite

1.
Wang Q, Li Y, Niu X, Zhang C, Zhang J, Cao J, Wu L. SNORD3A acts as a potential prognostic and therapeutic biomarker in gastric cancer. Electron. J. Biotechnol. [Internet]. 2024 Apr. 17 [cited 2024 Nov. 13];67:1-12. Available from: https://www.ejbiotechnology.info/index.php/ejbiotechnology/article/view/2023.08.004

Abstract

Background: Although SNORD3A has been implicated in cancer progression, its specific roles and underlying mechanisms in gastric cancer (GC) remain poorly understood. We analysed SNORD3A expression using TCGA data and evaluated patient survival via Kaplan‒Meier curves. Additionally, we conducted GO-KEGG enrichment analysis to identify relevant biological processes and signaling pathways, while ssGSEA was used to assess the correlation between SNORD3A and cancer immune infiltrates. Furthermore, we explored the relationship between SNORD3A and immunotherapy response through TIDE. We verified SNORD3A expression using real-time qPCR and assessed cell proliferation, migration, and invasion via CCK8 and Transwell migration and invasion assays.

Results: Our results revealed that SNORD3A was significantly upregulated in GC, with high expression correlating with poor survival. SNORD3A and related genes were primarily enriched in the insulin/insulin-related growth factor signaling pathway. We also observed negative associations between SNORD3A expression and several immune cells, including activated dendritic cells, CD56bright natural killer cells, central memory CD8 T cells, effector memory CD8 T cells, effector memory CD4 T cells, eosinophils, immature dendritic cells, macrophages, mast cells, MDSCs, memory B cells, monocytes, neutrophil cells, plasmacytoid dendritic cells, regulatory T cells, and T follicular helper cells. High SNORD3A expression also correlated with a poorer response to immunotherapy. Finally, inhibition of SNORD3A suppressed cell proliferation, migration, and invasion.

Conclusions: Our findings suggest that SNORD3A plays a catalytic role in the proliferation, migration and invasiveness of GC and may have potential as a diagnostic biomarker and therapeutic target for GC.

https://doi.org/10.1016/j.ejbt.2023.08.004
PDF
HTML

References

Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin 2021;71(3):209-249. https://doi.org/10.3322/caac.21660. PMID:33538338

Ajani JA, D'Amico TA, Bentrem DJ, et al. Gastric Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2022;20(2):167-192. https://doi.org/10.6004/jnccn.2022.0008. PMID:35130500

Smyth EC, Nilsson M, Grabsch HI, et al. Gastric cancer. Lancet 2020;396(10251):635-648. https://doi.org/10.1016/s0140-6736(20)31288-5. PMID:32861308

Tsao SW, Tsang CM, Pang PS, et al. The biology of EBV infection in human epithelial cells. Semin Cancer Biol 2012;22(2):137-43. https://doi.org/10.1016/j.semcancer.2012.02.004. PMID:22497025

Li GZ, Doherty GM, Wang J. Surgical Management of Gastric Cancer: A Review. JAMA Surg 2022;157(5):446-454. https://doi.org/10.1001/jamasurg.2022.0182. PMID:35319717

Alsina M, Arrazubi V, Diez M, et al. Current developments in gastric cancer: from molecular profiling to treatment strategy. Nat Rev Gastroenterol Hepatol 2022. https://doi.org/10.1038/s41575-022-00703-w. PMID:36344677

Zhang X, Wang C, Xia S, et al. The emerging role of snoRNAs in human disease. Genes & diseases 2023;10(5):2064-2081. https://doi.org/10.1016/j.gendis.2022.11.018. PMID:MEDLINE:37492704

Roychowdhury A, Samadder S, Das P, et al. Deregulation of H19 is associated with cervical carcinoma. Genomics 2020;112(1):961-970. https://doi.org/10.1016/j.ygeno.2019.06.012. PMID:31229557

Luo L, Zhang J, Tang H, et al. LncRNA SNORD3A specifically sensitizes breast cancer cells to 5-FU by sponging miR-185-5p to enhance UMPS expression. Cell Death Dis 2020;11(5):329. https://doi.org/10.1038/s41419-020-2557-2. PMID:32382150

Godel M, Morena D, Ananthanarayanan P, et al. Small Nucleolar RNAs Determine Resistance to Doxorubicin in Human Osteosarcoma. Int J Mol Sci 2020;21(12). https://doi.org/10.3390/ijms21124500. PMID:32599901

Luo LY, Zhang JL, Tang HL, et al. LncRNA SNORD3A specifically sensitizes breast cancer cells to 5-FU by sponging miR-185-5p to enhance UMPS expression. Cell Death & Disease 2020;11(5). https://doi.org/10.1038/s41419-020-2557-2. PMID:WOS:000533894200007

Wang G, Lu M, Yao Y, et al. Esculetin exerts antitumor effect on human gastric cancer cells through IGF-1/PI3K/Akt signaling pathway. Eur J Pharmacol 2017;814(207-215. https://doi.org/10.1016/j.ejphar.2017.08.025. PMID:28847482

Guo C, Chu H, Gong Z, et al. HOXB13 promotes gastric cancer cell migration and invasion via IGF-1R upregulation and subsequent activation of PI3K/AKT/mTOR signaling pathway. Life Sci 2021;278(119522. https://doi.org/10.1016/j.lfs.2021.119522. PMID:33894267

Kim R, An M, Lee H, et al. Early Tumor-Immune Microenvironmental Remodeling and Response to First-Line Fluoropyrimidine and Platinum Chemotherapy in Advanced Gastric Cancer. Cancer Discov 2022;12(4):984-1001. https://doi.org/10.1158/2159-8290.Cd-21-0888. PMID:34933901

Shi T, Zhang Y, Wang Y, et al. DKK1 Promotes Tumor Immune Evasion and Impedes Anti-PD-1 Treatment by Inducing Immunosuppressive Macrophages in Gastric Cancer. Cancer Immunol Res 2022;10(12):1506-1524. https://doi.org/10.1158/2326-6066.Cir-22-0218. PMID:36206576

Gambardella V, Castillo J, Tarazona N, et al. The role of tumor-associated macrophages in gastric cancer development and their potential as a therapeutic target. Cancer Treat Rev 2020;86(102015. https://doi.org/10.1016/j.ctrv.2020.102015. PMID:32248000

Saisana M, Griffin SM, May FEB. Importance of the type I insulin-like growth factor receptor in HER2, FGFR2 and MET-unamplified gastric cancer with and without Ras pathway activation. Oncotarget 2016;7(34):54445-54462. https://doi.org/10.18632/oncotarget.10642. PMID:WOS:000385435000029

Choi YJ. Insulin Resistance: A Hidden Risk Factor for Gastric Cancer? Gut and Liver 2019;13(2):133-134. https://doi.org/10.5009/gnl19060. PMID:WOS:000461020800001

Lee JS, Lero MW, Mercado-Matos J, et al. The insulin and IGF signaling pathway sustains breast cancer stem cells by IRS2/PI3K-mediated regulation of MYC. Cell Rep 2022;41(10):111759. https://doi.org/10.1016/j.celrep.2022.111759. PMID:36476848

Zhen N, Gu S, Ma J, et al. CircHMGCS1 Promotes Hepatoblastoma Cell Proliferation by Regulating the IGF Signaling Pathway and Glutaminolysis. Theranostics 2019;9(3):900-919. https://doi.org/10.7150/thno.29515. PMID:30809316

Du J, Shi HR, Ren F, et al. Inhibition of the IGF signaling pathway reverses cisplatin resistance in ovarian cancer cells. BMC Cancer 2017;17(1):851. https://doi.org/10.1186/s12885-017-3840-1. PMID:29241458

Saisana M, Griffin SM, May FEB. Insulin and the insulin receptor collaborate to promote human gastric cancer. Gastric Cancer 2022;25(1):107-123. https://doi.org/10.1007/s10120-021-01236-y. PMID:34554347

Jeong I, Kang SK, Kwon WS, et al. Regulation of proliferation and invasion by the IGF signalling pathway in Epstein-Barr virus-positive gastric cancer. J Cell Mol Med 2018;22(12):5899-5908. https://doi.org/10.1111/jcmm.13859. PMID:30247804

Zavros Y, Merchant JL. The immune microenvironment in gastric adenocarcinoma. Nat Rev Gastroenterol Hepatol 2022;19(7):451-467. https://doi.org/10.1038/s41575-022-00591-0. PMID:35288702

Joshi SS, Badgwell BD. Current treatment and recent progress in gastric cancer. CA Cancer J Clin 2021;71(3):264-279. https://doi.org/10.3322/caac.21657. PMID:33592120

Lei ZN, Teng QX, Tian Q, et al. Signaling pathways and therapeutic interventions in gastric cancer. Signal Transduct Target Ther 2022;7(1):358. https://doi.org/10.1038/s41392-022-01190-w. PMID:36209270

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Copyright (c) 2024 Electronic Journal of Biotechnology