Login Register Cart 0
Generic placeholder image

Current Cancer Drug Targets

Editor-in-Chief

ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Protein Arginine Methyltransferases 5 (PRMT5) affect Multiple Stages of Autophagy and Modulate Autophagy-related Genes in Controlling Breast Cancer Tumorigenesis

Author(s): Jing Kong, Zhe Wang, Yong Zhang, Ting Wang and Rui Ling*

Volume 23, Issue 3, 2023

Published on: 27 October, 2022

Page: [242 - 250] Pages: 9

DOI: 10.2174/1568009622666220922093059

Price: $65

Abstract

Background: Autophagy disorders are linked to human cancer, and the details of their mechanisms remain unclear.

Objective: To investigate the regulatory role of PRMT5 in the autophagy of breast cancer cells.

Methods: Human breast adenocarcinoma cell lines (MDA-MB-231, MCF7) were cultured. Plasmids of overexpression and down-regulation of PRMT5 were transfected into MDA-MB-231 and MCF7 cells. The MTT assay was used to determine the proliferation of MDA-MB-231 and MCF7 cells. A western blotting assay was used to verify the expression of autophagy-associated molecules. Immunofluorescence was applied to observe the expression of GFP-LC3.

Results: The expression of PRMT5 decreased the sensitivity to rapamycin and nutrient deprivation. PRMT5 acts as an oncogene to promote cell proliferation and influences migration and stamness. PRMT5 expression elevated the autophagic activity initiated by EBSS and Rapamycin. PRMT5 was necessary and sufficient to enhance stress-induced autophagy. PRMT5 could improve several autophagy- related gene expressions. Atg5 expression could be regulated by activating the PRMT5 and PDCD4 molecules. The PRMT5 molecule could mediate the regulation of ULK1 expression.

Conclusion: PRMT5 influenced multiple stages of autophagy in controlling autophagy and tumorigenesis. Autophagy-related PRMT5 might be a respected target for therapeutic interventions in cancers. This study would provide new ideas for treating and selecting breast cancer targets.

Keywords: PRMT5, autophagy, ULK1, Atg5, breast cancer cell

« Previous
Graphical Abstract

[1]
Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics, 2018. CA Cancer J. Clin., 2018, 68(1), 7-30.
[http://dx.doi.org/10.3322/caac.21442] [PMID: 29313949]
[2]
Karamat, U.; Ejaz, S. Overexpression of RAD50 is the marker of poor prognosis and drug resistance in breast cancer patients. Curr. Cancer Drug Targets, 2021, 21(2), 163-176.
[http://dx.doi.org/10.2174/1568009620666201009125507] [PMID: 33038913]
[3]
Jin, G.; Wang, K.; Liu, Y.; Liu, X.; Zhang, X.; Zhang, H. Proteomic level changes on treatment in MCF-7/DDP breast cancer drug- resistant cells. Anticancer. Agents Med. Chem., 2020, 20(6), 687-699.
[http://dx.doi.org/10.2174/1871520620666200213102849] [PMID: 32053082]
[4]
Mizushima, N.; Komatsu, M. Autophagy: Renovation of cells and tissues. Cell, 2011, 147(4), 728-741.
[http://dx.doi.org/10.1016/j.cell.2011.10.026] [PMID: 22078875]
[5]
Mathew, R.; Karantza-Wadsworth, V.; White, E. Role of autophagy in cancer. Nat. Rev. Cancer, 2007, 7(12), 961-967.
[http://dx.doi.org/10.1038/nrc2254] [PMID: 17972889]
[6]
Shimizu, S.; Yoshida, T.; Tsujioka, M.; Arakawa, S. Autophagic cell death and cancer. Int. J. Mol. Sci., 2014, 15(2), 3145-3153.
[http://dx.doi.org/10.3390/ijms15023145] [PMID: 24566140]
[7]
Stopa, N.; Krebs, J.E.; Shechter, D. The PRMT5 arginine methyltransferase: Many roles in development, cancer and beyond. Cell. Mol. Life Sci., 2015, 72(11), 2041-2059.
[http://dx.doi.org/10.1007/s00018-015-1847-9] [PMID: 25662273]
[8]
Hu, D.; Gur, M.; Zhou, Z.; Gamper, A.; Hung, M.C.; Fujita, N.; Lan, L.; Bahar, I.; Wan, Y. Interplay between arginine methylation and ubiquitylation regulates KLF4-mediated genome stability and carcinogenesis. Nat. Commun., 2015, 6(1), 8419.
[http://dx.doi.org/10.1038/ncomms9419] [PMID: 26420673]
[9]
Gu, Z.; Gao, S.; Zhang, F.; Wang, Z.; Ma, W.; Davis, R.E.; Wang, Z. Protein arginine methyltransferase 5 is essential for growth of lung cancer cells. Biochem. J., 2012, 446(2), 235-241.
[http://dx.doi.org/10.1042/BJ20120768] [PMID: 22708516]
[10]
Powers, M.A.; Fay, M.M.; Factor, R.E.; Welm, A.L.; Ullman, K.S. Protein arginine methyltransferase 5 accelerates tumor growth by arginine methylation of the tumor suppressor programmed cell death 4. Cancer Res., 2011, 71(16), 5579-5587.
[http://dx.doi.org/10.1158/0008-5472.CAN-11-0458] [PMID: 21700716]
[11]
Wang, Z.; Kong, J.; Wu, Y.; Zhang, J.; Wang, T.; Li, N.; Fan, J.; Wang, H.; Zhang, J.; Ling, R. PRMT5 determines the sensitivity to chemotherapeutics by governing stemness in breast cancer. Breast Cancer Res. Treat., 2018, 168(2), 531-542.
[http://dx.doi.org/10.1007/s10549-017-4597-6] [PMID: 29185119]
[12]
Sheng, X.; Wang, Z. Protein arginine methyltransferase 5 regulates multiple signaling pathways to promote lung cancer cell proliferation. BMC Cancer, 2016, 16(1), 567.
[http://dx.doi.org/10.1186/s12885-016-2632-3] [PMID: 27480244]
[13]
Jiang, H.; Zhu, Y.; Zhou, Z.; Xu, J.; Jin, S.; Xu, K.; Zhang, H.; Sun, Q.; Wang, J.; Xu, J. PRMT5 promotes cell proliferation by inhibiting BTG2 expression via the ERK signaling pathway in hepatocellular carcinoma. Cancer Med., 2018, 7(3), 869-882.
[http://dx.doi.org/10.1002/cam4.1360] [PMID: 29441724]
[14]
Chen, H.; Lorton, B.; Gupta, V.; Shechter, D.A. TGFβ-PRMT5-MEP50 axis regulates cancer cell invasion through histone H3 and H4 arginine methylation coupled transcriptional activation and repression. Oncogene, 2017, 36(3), 373-386.
[http://dx.doi.org/10.1038/onc.2016.205] [PMID: 27270440]
[15]
Wu, Y.; Wang, Z.; Zhang, J.; Ling, R. Elevated expression of protein arginine methyltransferase 5 predicts the poor prognosis of breast cancer. Tumour Biol., 2017, 39(4)
[http://dx.doi.org/10.1177/1010428317695917] [PMID: 28381188]
[16]
Huang, S.; Chi, Y.; Qin, Y.; Wang, Z.; Xiu, B.; Su, Y.; Guo, R.; Guo, L.; Sun, H.; Zeng, C.; Zhou, S.; Hu, X.; Liu, S.; Shao, Z.; Wu, Z.; Jin, W.; Wu, J. CAPG enhances breast cancer metastasis by competing with PRMT5 to modulate STC-1 transcription. Theranostics, 2018, 8(9), 2549-2564.
[http://dx.doi.org/10.7150/thno.22523] [PMID: 29721098]
[17]
Levine, B. Autophagy and cancer. Nature, 2007, 446(7137), 745-747.
[http://dx.doi.org/10.1038/446745a] [PMID: 17429391]
[18]
Itakura, E.; Kishi, C.; Inoue, K.; Mizushima, N. Beclin 1 forms two distinct phosphatidylinositol 3-kinase complexes with mammalian Atg14 and UVRAG. Mol. Biol. Cell, 2008, 19(12), 5360-5372.
[http://dx.doi.org/10.1091/mbc.e08-01-0080] [PMID: 18843052]
[19]
Jeon, S.M. Regulation and function of AMPK in physiology and diseases. Exp. Mol. Med., 2016, 48(7), e245.
[http://dx.doi.org/10.1038/emm.2016.81] [PMID: 27416781]
[20]
Kim, J.; Kundu, M.; Viollet, B.; Guan, K.L. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat. Cell Biol., 2011, 13(2), 132-141.
[http://dx.doi.org/10.1038/ncb2152] [PMID: 21258367]
[21]
Song, X.; Zhang, X.; Wang, X.; Zhu, F.; Guo, C.; Wang, Q.; Shi, Y.; Wang, J.; Chen, Y.; Zhang, L. Tumor suppressor gene PDCD4 negatively regulates autophagy by inhibiting the expression of autophagy-related gene ATG5. Autophagy, 2013, 9(5), 743-755.
[http://dx.doi.org/10.4161/auto.24069] [PMID: 23486359]
[22]
Fay, M.M.; Clegg, J.M.; Uchida, K.A.; Powers, M.A.; Ullman, K.S. Enhanced arginine methylation of programmed cell death 4 protein during nutrient deprivation promotes tumor cell viability. J. Biol. Chem., 2014, 289(25), 17541-17552.
[http://dx.doi.org/10.1074/jbc.M113.541300] [PMID: 24764298]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy