SiRNA-mediated Silencing of the RPS19 Gene Induces Apoptosis and Inhibits Cell Cycle Progression in Chronic Myeloid Leukemia Cells

Overview

Journal Int J Mol Cell Med

Date 2025 Feb 3

PMID 39895916

Authors

Javad Roodgar-Saffari

Vajiheh Zarrinpour

Mohammad Mahdi Forghanifard

Affiliations

Soon will be listed here.

Abstract

This research delves into the therapeutic implications of utilizing small interfering RNA (siRNA) to target the ribosomal protein S19 (RPS19) gene in chronic myeloid leukemia (CML) using the K562 cell line model. The primary objective was to investigate how gene silencing affects apoptosis promotion and cell cycle arrest. The study employed bioinformatics tools and databases to explore the interactions involving RPS19 and neighboring proteins. Subsequently, siRNA-mediated gene silencing was utilized to suppress RPS19 expression in K-562 cells, with assessments conducted on cell cycle progression and apoptosis through flow cytometry analysis. Furthermore, real-time PCR was employed to evaluate the expression levels of RPS19, along with the closely associated RPS16 and RPS18 genes. Silencing the RPS19 gene in siRNA-transfected K-562 cells led to an increase in apoptotic cells by over 20%, with a significant accumulation in the sub-G1 and G1 phases. Additionally, the knockdown of RPS19 resulted in a 75% decrease in RPS16 expression and a 50% decrease in RPS18 expression. These results demonstrate the therapeutic potential of targeting RPS19 in CML cells, suggesting a promising approach for precise treatment strategies in leukemia and potentially other types of cancer.

References

Kong L, Wei Q, Hu X, Chen L, Li J . Ribosomal protein small subunit 15A (RPS15A) inhibits the apoptosis of breast cancer MDA-MB-231 cells via upregulating phosphorylated ERK1/2, Bad, and Chk1. J Cell Biochem. 2019; 121(1):587-595. DOI: 10.1002/jcb.29304. View

Li C, Chen D, Luo M, Ge M, Zhu J . Knockdown of ribosomal protein L39 by RNA interference inhibits the growth of human pancreatic cancer cells in vitro and in vivo. Biotechnol J. 2014; 9(5):652-63. DOI: 10.1002/biot.201300321. View

Alam E, Maaliki L, Nasr Z . Ribosomal protein S3 selectively affects colon cancer growth by modulating the levels of p53 and lactate dehydrogenase. Mol Biol Rep. 2020; 47(8):6083-6090. DOI: 10.1007/s11033-020-05683-1. View

Kang J, Brajanovski N, Chan K, Xuan J, Pearson R, Sanij E . Ribosomal proteins and human diseases: molecular mechanisms and targeted therapy. Signal Transduct Target Ther. 2021; 6(1):323. PMC: 8405630. DOI: 10.1038/s41392-021-00728-8. View

Arthurs C, Murtaza B, Thomson C, Dickens K, Henrique R, Patel H . Expression of ribosomal proteins in normal and cancerous human prostate tissue. PLoS One. 2017; 12(10):e0186047. PMC: 5634644. DOI: 10.1371/journal.pone.0186047. View

Turi Z, Lacey M, Mistrik M, Moudry P . Impaired ribosome biogenesis: mechanisms and relevance to cancer and aging. Aging (Albany NY). 2019; 11(8):2512-2540. PMC: 6520011. DOI: 10.18632/aging.101922. View

Chen B, Tan Z, Gao J, Wu W, Liu L, Jin W . Hyperphosphorylation of ribosomal protein S6 predicts unfavorable clinical survival in non-small cell lung cancer. J Exp Clin Cancer Res. 2015; 34:126. PMC: 4618148. DOI: 10.1186/s13046-015-0239-1. View

Vysochinskaya V, Dovbysh O, Gorshkov A, Brodskaia A, Dubina M, Vasin A . Advancements and Future Prospects in Molecular Targeted and siRNA Therapies for Chronic Myeloid Leukemia. Biomolecules. 2024; 14(6). PMC: 11201692. DOI: 10.3390/biom14060644. View

Sampaio M, Santos M, Marques H, Lima de Souza Goncalves V, Araujo G, Lopes L . Chronic myeloid leukemia-from the Philadelphia chromosome to specific target drugs: A literature review. World J Clin Oncol. 2021; 12(2):69-94. PMC: 7918527. DOI: 10.5306/wjco.v12.i2.69. View

10.

Wang W, Nag S, Zhang X, Wang M, Wang H, Zhou J . Ribosomal proteins and human diseases: pathogenesis, molecular mechanisms, and therapeutic implications. Med Res Rev. 2014; 35(2):225-85. PMC: 4710177. DOI: 10.1002/med.21327. View

11.

Muro S, Miyake Y, Kato H, Tsutsumi K, Yamamoto K . Serum anti-60S ribosomal protein L29 antibody as a novel prognostic marker for unresectable pancreatic cancer. Digestion. 2015; 91(2):164-73. DOI: 10.1159/000371545. View

12.

Yang S, Cui J, Yang Y, Liu Z, Yan H, Tang C . Over-expressed RPL34 promotes malignant proliferation of non-small cell lung cancer cells. Gene. 2015; 576(1 Pt 3):421-8. DOI: 10.1016/j.gene.2015.10.053. View

13.

El Khoury W, Nasr Z . Deregulation of ribosomal proteins in human cancers. Biosci Rep. 2021; 41(12). PMC: 8685657. DOI: 10.1042/BSR20211577. View

14.

Goudarzi K, Lindstrom M . Role of ribosomal protein mutations in tumor development (Review). Int J Oncol. 2016; 48(4):1313-24. PMC: 4777597. DOI: 10.3892/ijo.2016.3387. View

15.

Livak K, Schmittgen T . Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2002; 25(4):402-8. DOI: 10.1006/meth.2001.1262. View

16.

Daskalakis M, Feller A, Noetzli J, Bonadies N, Arndt V, Baerlocher G . Potential to Improve Therapy of Chronic Myeloid Leukemia (CML), Especially for Patients with Older Age: Incidence, Mortality, and Survival Rates of Patients with CML in Switzerland from 1995 to 2017. Cancers (Basel). 2021; 13(24). PMC: 8699480. DOI: 10.3390/cancers13246269. View

17.

Choesmel V, Bacqueville D, Rouquette J, Noaillac-Depeyre J, Fribourg S, Cretien A . Impaired ribosome biogenesis in Diamond-Blackfan anemia. Blood. 2006; 109(3):1275-83. PMC: 1785132. DOI: 10.1182/blood-2006-07-038372. View

18.

Campagnoli M, Ramenghi U, Armiraglio M, Quarello P, Garelli E, Carando A . RPS19 mutations in patients with Diamond-Blackfan anemia. Hum Mutat. 2008; 29(7):911-20. DOI: 10.1002/humu.20752. View

19.

Ono H, Iizumi Y, Goi W, Sowa Y, Taguchi T, Sakai T . Ribosomal protein S3 regulates XIAP expression independently of the NF-κB pathway in breast cancer cells. Oncol Rep. 2017; 38(5):3205-3210. DOI: 10.3892/or.2017.6008. View

20.

Wei F, Ding L, Wei Z, Zhang Y, Li Y, Qinghua L . Ribosomal protein L34 promotes the proliferation, invasion and metastasis of pancreatic cancer cells. Oncotarget. 2016; 7(51):85259-85272. PMC: 5356734. DOI: 10.18632/oncotarget.13269. View