Comprehensive Analysis of M6A Regulators Prognostic Value in Prostate Cancer

Overview

Journal Aging (Albany NY)

Specialty Geriatrics

Date 2020 Jul 26

PMID 32710725

Citations 37

Authors

Guangjie Ji

Cong Huang

Shiming He

Yanqing Gong

Gang Song

Xuesong Li

Liqun Zhou

Affiliations

Soon will be listed here.

Abstract

Background: N6-methyladenosine (m6A) is the most prevalent RNA modification. While the role of m6A in prostate cancer remains unknown. We aim to measure the effects of m6A methylation regulatory genes during the development and progression of prostate cancer.

Methods: We collected transcriptome information and gene-level alteration data from The Cancer Genome Atlas datasets. The log-rank test and Cox regression model were used to examine the prognosis value of m6A methylation regulatory genes of prostate cancer.

Results: We discovered that most of m6A methylation regulators were highly expressed in aggressive prostate cancer. Univariable and multivariable Cox regression results showed that the expression of Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1) and N6-adenosine-methyltransferase non-catalytic subunit (METTL14) and copy number variant of AlkB Homolog 5 (ALKBH5) were considerably associated with a recurrence-free survival of prostate cancer. Furthermore, a high level of m6A methylation in mRNA promotes the progression of prostate cancer via regulating subcellular protein localization.

Conclusion: Patients with a high level of mRNA methylation resulted from overexpression of reader proteins and methyltransferase complexes had poor survival benefits through influencing protein subcellular location in prostate cancer.

Citing Articles

Stabilization of RRBP1 mRNA via an mA-dependent manner in prostate cancer constitutes a therapeutic vulnerability amenable to small-peptide inhibition of METTL3.

Feng Y, Li Z, Zhu J, Zou C, Tian Y, Xiong J Cell Mol Life Sci. 2024; 81(1):414.

PMID: 39367907 PMC: 11455910. DOI: 10.1007/s00018-024-05418-6.

Dendrobine alleviates oleic acid-induced lipid accumulation by inhibiting FOS/METTL14 pathway.

Zhang J, Zhang H, Chen Y, Chen S, Liu H J Mol Histol. 2024; 55(5):995-1007.

PMID: 39136847 DOI: 10.1007/s10735-024-10246-w.

Androgen Signaling in Prostate Cancer: When a Friend Turns Foe.

Pandey S, Sabharwal U, Tripathi S, Mishra A, Yadav N, Dwivedi-Agnihotri H Endocr Metab Immune Disord Drug Targets. 2024; 25(1):37-56.

PMID: 38831575 DOI: 10.2174/0118715303313528240523101940.

Role of N‑methyladenosine in the pathogenesis, diagnosis and treatment of prostate cancer (Review).

Pan J, Tong F, Ren N, Ren L, Yang Y, Gao F Oncol Rep. 2024; 51(6).

PMID: 38757383 PMC: 11110010. DOI: 10.3892/or.2024.8747.

RNA m6a Methylation Regulator Expression in Castration-Resistant Prostate Cancer Progression and Its Genetic Associations.

Liyanage C, Fernando A, Chamberlain A, Moradi A, Batra J Cancers (Basel). 2024; 16(7).

PMID: 38610981 PMC: 11011207. DOI: 10.3390/cancers16071303.

References

Goodarzi H, Najafabadi H, Oikonomou P, Greco T, Fish L, Salavati R . Systematic discovery of structural elements governing stability of mammalian messenger RNAs. Nature. 2012; 485(7397):264-8. PMC: 3350620. DOI: 10.1038/nature11013. View

Wang Y, Li Y, Yue M, Wang J, Kumar S, Wechsler-Reya R . N-methyladenosine RNA modification regulates embryonic neural stem cell self-renewal through histone modifications. Nat Neurosci. 2018; 21(2):195-206. PMC: 6317335. DOI: 10.1038/s41593-017-0057-1. View

Barcelo C, Etchin J, Mansour M, Sanda T, Ginesta M, Sanchez-Arevalo Lobo V . Ribonucleoprotein HNRNPA2B1 interacts with and regulates oncogenic KRAS in pancreatic ductal adenocarcinoma cells. Gastroenterology. 2014; 147(4):882-892.e8. DOI: 10.1053/j.gastro.2014.06.041. View

Liu J, Ren D, Du Z, Wang H, Zhang H, Jin Y . mA demethylase FTO facilitates tumor progression in lung squamous cell carcinoma by regulating MZF1 expression. Biochem Biophys Res Commun. 2018; 502(4):456-464. DOI: 10.1016/j.bbrc.2018.05.175. View

Cai J, Yang F, Zhan H, Situ J, Li W, Mao Y . RNA mA Methyltransferase METTL3 Promotes The Growth Of Prostate Cancer By Regulating Hedgehog Pathway. Onco Targets Ther. 2019; 12:9143-9152. PMC: 6842310. DOI: 10.2147/OTT.S226796. View

Chen M, Wei L, Law C, Tsang F, Shen J, Cheng C . RNA N6-methyladenosine methyltransferase-like 3 promotes liver cancer progression through YTHDF2-dependent posttranscriptional silencing of SOCS2. Hepatology. 2017; 67(6):2254-2270. DOI: 10.1002/hep.29683. View

Muller S, Glass M, Singh A, Haase J, Bley N, Fuchs T . IGF2BP1 promotes SRF-dependent transcription in cancer in a m6A- and miRNA-dependent manner. Nucleic Acids Res. 2018; 47(1):375-390. PMC: 6326824. DOI: 10.1093/nar/gky1012. View

Antonarakis E, Lu C, Wang H, Luber B, Nakazawa M, Roeser J . AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer. N Engl J Med. 2014; 371(11):1028-38. PMC: 4201502. DOI: 10.1056/NEJMoa1315815. View

Huang H, Weng H, Sun W, Qin X, Shi H, Wu H . Recognition of RNA N-methyladenosine by IGF2BP proteins enhances mRNA stability and translation. Nat Cell Biol. 2018; 20(3):285-295. PMC: 5826585. DOI: 10.1038/s41556-018-0045-z. View

10.

Zhang C, Samanta D, Lu H, Bullen J, Zhang H, Chen I . Hypoxia induces the breast cancer stem cell phenotype by HIF-dependent and ALKBH5-mediated m⁶A-demethylation of NANOG mRNA. Proc Natl Acad Sci U S A. 2016; 113(14):E2047-56. PMC: 4833258. DOI: 10.1073/pnas.1602883113. View

11.

Weng H, Huang H, Wu H, Qin X, Zhao B, Dong L . METTL14 Inhibits Hematopoietic Stem/Progenitor Differentiation and Promotes Leukemogenesis via mRNA mA Modification. Cell Stem Cell. 2018; 22(2):191-205.e9. PMC: 5860916. DOI: 10.1016/j.stem.2017.11.016. View

12.

Lin S, Choe J, Du P, Triboulet R, Gregory R . The m(6)A Methyltransferase METTL3 Promotes Translation in Human Cancer Cells. Mol Cell. 2016; 62(3):335-345. PMC: 4860043. DOI: 10.1016/j.molcel.2016.03.021. View

13.

Yang Y, Wei Q, Tang Y, Wang Y, Luo Q, Zhao H . Loss of hnRNPA2B1 inhibits malignant capability and promotes apoptosis via down-regulating Lin28B expression in ovarian cancer. Cancer Lett. 2020; 475:43-52. DOI: 10.1016/j.canlet.2020.01.029. View

14.

Jiang Z, Chu P, Woda B, Rock K, Liu Q, Hsieh C . Analysis of RNA-binding protein IMP3 to predict metastasis and prognosis of renal-cell carcinoma: a retrospective study. Lancet Oncol. 2006; 7(7):556-64. DOI: 10.1016/S1470-2045(06)70732-X. View

15.

Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M . Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2014; 136(5):E359-86. DOI: 10.1002/ijc.29210. View

16.

Szarvas T, Tschirdewahn S, Niedworok C, Kramer G, Sevcenco S, Reis H . Prognostic value of tissue and circulating levels of IMP3 in prostate cancer. Int J Cancer. 2014; 135(7):1596-604. DOI: 10.1002/ijc.28808. View

17.

Liu J, Eckert M, Harada B, Liu S, Lu Z, Yu K . mA mRNA methylation regulates AKT activity to promote the proliferation and tumorigenicity of endometrial cancer. Nat Cell Biol. 2018; 20(9):1074-1083. PMC: 6245953. DOI: 10.1038/s41556-018-0174-4. View

18.

Barbieri I, Tzelepis K, Pandolfini L, Shi J, Millan-Zambrano G, Robson S . Promoter-bound METTL3 maintains myeloid leukaemia by mA-dependent translation control. Nature. 2017; 552(7683):126-131. PMC: 6217924. DOI: 10.1038/nature24678. View

19.

Freiberger C, Berneking V, Vogeli T, Kirschner-Hermanns R, Eble M, Pinkawa M . Long-term prognostic significance of rising PSA levels following radiotherapy for localized prostate cancer - focus on overall survival. Radiat Oncol. 2017; 12(1):98. PMC: 5471896. DOI: 10.1186/s13014-017-0837-5. View

20.

Zhou Y, Huang T, Siu H, Wong C, Dong Y, Wu F . IGF2BP3 functions as a potential oncogene and is a crucial target of miR-34a in gastric carcinogenesis. Mol Cancer. 2017; 16(1):77. PMC: 5387209. DOI: 10.1186/s12943-017-0647-2. View