Non-coding RNA-Mediated N6-Methyladenosine (m6A) deposition: A pivotal regulator of cancer, impacting key signaling pathways in carcinogenesis and therapy response

Mehrdad Hashemi; Pouria Daneii; Mohammad Arad Zandieh; Rasoul Raesi; Neda Zahmatkesh; Mehrsa Bayat; Anwar Abuelrub; Zeinab Khazaei Koohpar; Amir Reza Aref; Ali Zarrabi; Mohsen Rashidi; Shokooh Salimimoghadam; Maliheh Entezari; Afshin Taheriazam; Ramin Khorrami

doi:10.1016/j.ncrna.2023.11.005

Non-coding RNA-Mediated N6-Methyladenosine (m⁶A) deposition: A pivotal regulator of cancer, impacting key signaling pathways in carcinogenesis and therapy response

Noncoding RNA Res. 2023 Nov 13;9(1):84-104. doi: 10.1016/j.ncrna.2023.11.005. eCollection 2024 Mar.

Authors

Mehrdad Hashemi^{1

2}, Pouria Daneii¹, Mohammad Arad Zandieh³, Rasoul Raesi^{4

5}, Neda Zahmatkesh⁶, Mehrsa Bayat⁷, Anwar Abuelrub⁸, Zeinab Khazaei Koohpar⁹, Amir Reza Aref¹⁰, Ali Zarrabi¹¹, Mohsen Rashidi^{12

13}, Shokooh Salimimoghadam¹⁴, Maliheh Entezari^{1

2}, Afshin Taheriazam^{1

15}, Ramin Khorrami¹⁶

Affiliations

¹ Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
² Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
³ Department of Food Hygiene and Quality Control, Division of Epidemiology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
⁴ Department of Health Services Management, Mashhad University of Medical Sciences, Mashhad, Iran.
⁵ Department of Medical-Surgical Nursing, Mashhad University of Medical Sciences, Mashhad, Iran.
⁶ Department of Genetics, Zanjan Branch, Islamic Azad University, Zanjan, Iran.
⁷ Department of Health Sciences, Bahcesehir University, Istanbul, Turkey.
⁸ Neuroscience Laboratory, Health Sciences Institute, Bahcesehir University, Istanbul, Turkey.
⁹ Department of Cell and Molecular Biology, Faculty of Biological Sciences, Tonekabon Branch, Islamic Azad University, Tonekabon, Iran.
¹⁰ Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
¹¹ Department of Biomedical Engineering, Faculty of Engineering and Natural Sciences, Istinye University, Istanbul, 34396, Turkey.
¹² Department Pharmacology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
¹³ The Health of Plant and Livestock Products Research Center, Mazandaran University of Medical Sciences, Sari, Iran.
¹⁴ Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran.
¹⁵ Department of Orthopedics, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
¹⁶ Department of Food Hygiene and Quality Control, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.

Abstract

The emergence of RNA modifications has recently been considered as critical post-transcriptional regulations which governed gene expression. N⁶-methyladenosine (m⁶A) modification is the most abundant type of RNA modification which is mediated by three distinct classes of proteins called m⁶A writers, readers, and erasers. Accumulating evidence has been made in understanding the role of m⁶A modification of non-coding RNAs (ncRNAs) in cancer. Importantly, aberrant expression of ncRNAs and m⁶A regulators has been elucidated in various cancers. As the key role of ncRNAs in regulation of cancer hallmarks is well accepted now, it could be accepted that m⁶A modification of ncRNAs could affect cancer progression. The present review intended to discuss the latest knowledge and importance of m⁶A epigenetic regulation of ncRNAs including mircoRNAs, long non-coding RNAs, and circular RNAs, and their interaction in the context of cancer. Moreover, the current insight into the underlying mechanisms of therapy resistance and also immune response and escape mediated by m⁶A regulators and ncRNAs are discussed.

Keywords: Cancer; Immune response; circRNA; lncRNA; m6A; miRNA.

Publication types

Review