Chemical modifications of RNA molecules, resembling m6A, can critically impact gene expression, influencing various facets of cancer development and progression. Nonetheless, while studies into m6A modification of messenger RNA (mRNA) have been extensive, exploration of its impact on lncRNAs, especially inside the context of PDAC, has been relatively limited.

In an modern study published within the Genes & Diseases journal, a team from The Kid’s Hospital, Zhejiang University School of Medicine, People’s Hospital of Hangzhou Medical College and University of Mississippi Medical Center employed a methylated RNA immunoprecipitation (MeRIP) technique to uncover the role of LINC00901, an m6A-modified long noncoding RNA (lncRNA), in promoting the proliferation, survival, and invasiveness of pancreatic ductal adenocarcinoma (PDAC) cells, thus resulting in tumor growth. Intriguingly, the study suggests that the m6A reader protein YTHDF1 negatively regulates LINC00901 expression. The team identified two m6A sites on LINC00901 essential for its interaction with YTHDF1. Their function was underscored when mutations at these sites reduced interaction, thereby emphasizing the importance of m6A modification in LINC00901’s oncogenic role. The study further unveils a critical LINC00901-IGF2BP2-MYC axis, driving PDAC progression in an m6A-dependent manner, thereby illuminating a possible latest therapeutic goal. The researchers suggest the m6A machinery as a promising therapeutic avenue, hinting on the potential for improved patient response to treatment through combining a checkpoint inhibitor with YTHDF1 deficiency. Furthermore, with m6A modification implicated within the regulation of each innate and adaptive immune cells, the opportunity of developing immunotherapies targeting this pathway emerges.

This study marks a major advancement in understanding how RNA modifications, resembling m6A, impact gene expression and contribute to cancer development. These findings offer fresh insights into the role of m6A modification in lncRNA within the context of PDAC, enhancing our understanding of the disease’s progression and opening up potential latest pathways for treatment. By exploring this RNA modification, the research expands the horizon of possibilities for targeted cancer therapies.

Source:

Chongqing Medical University

Journal reference:

Peng, W-X., et al. (2023) N6-methyladenosine modified LINC00901 promotes pancreatic cancer progression through IGF2BP2/MYC axis. Genes & Diseases. doi.org/10.1016/j.gendis.2022.02.014.