VIRMA, also known as KIAA1429, is a key component of the N6-methyladenosine (m6A) methyltransferase complex. m6A is an abundant and conserved internal cotranscriptional modification in eukaryotic RNAs, playing crucial roles in RNA functions, tissue development, and disease processes. VIRMA is involved in mediating preferential m6A mRNA methylation in the 3'untranslated region (3'UTR) and near stop codons, and is associated with alternative polyadenylation [1].

Functional studies have revealed its significance in multiple cancers. In nasopharyngeal carcinoma (NPC), VIRMA is upregulated and promotes tumorigenesis and metastasis by mediating m6A methylation of E2F7 3'-UTR, which increases E2F7 mRNA stability [2]. In triple-negative breast cancer (TNBC), VIRMA promotes progression by upregulating m6A-dependent KIF15 expression [3]. In breast cancer, it promotes cancer progression through m6A-dependent cytosolic HAS2 stabilization [4]. In non-small cell lung cancer (NSCLC), VIRMA-guided m6A modifications promote cancer progression via m6A-dependent degradation of DAPK3 mRNA [6]. In intrahepatic cholangiocarcinoma (ICC), VIRMA is highly expressed, and it promotes ICC proliferation and metastasis by stabilizing TMED2 and PARD3B expression through the m6A-HuR-mediated mechanism [5].

In conclusion, VIRMA is a vital player in m6A-mediated mRNA regulation. Its dysregulation in various cancers, as demonstrated through in vivo and in vitro functional studies, highlights its potential as a therapeutic target. Understanding VIRMA's role provides insights into the molecular mechanisms of cancer development and progression, which could potentially lead to new strategies for cancer treatment.

References:

1. Yue, Yanan, Liu, Jun, Cui, Xiaolong, He, Chuan, Liu, Jianzhao. 2018. VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. In Cell discovery, 4, 10. doi:10.1038/s41421-018-0019-0. https://pubmed.ncbi.nlm.nih.gov/29507755/

2. Zheng, Zi-Qi, Huang, Zhuo-Hui, Liang, Ye-Lin, Tang, Ling-Long, Wei, Denghui. 2023. VIRMA promotes nasopharyngeal carcinoma, tumorigenesis, and metastasis by upregulation of E2F7 in an m6A-dependent manner. In The Journal of biological chemistry, 299, 104677. doi:10.1016/j.jbc.2023.104677. https://pubmed.ncbi.nlm.nih.gov/37028765/

3. Chen, Chunchun, Wang, Yanyan, Li, Yulong, Zhang, Chao. . VIRMA Facilitates Triple-Negative Breast Cancer Progression via Increasing m6A-Dependent KIF15 Expression. In Discovery medicine, 35, 787-795. doi:10.24976/Discov.Med.202335178.73. https://pubmed.ncbi.nlm.nih.gov/37811616/

4. Li, Na, Zhu, Zhouting, Deng, Yufei, Kang, Yuqi, Rana, Tariq M. 2023. KIAA1429/VIRMA promotes breast cancer progression by m6 A-dependent cytosolic HAS2 stabilization. In EMBO reports, 24, e55506. doi:10.15252/embr.202255506. https://pubmed.ncbi.nlm.nih.gov/37705505/

5. Xu, Hongfa, Lin, Xiaowen, Li, Zhongliang, Zhan, Meixiao, He, Ke. 2023. VIRMA facilitates intrahepatic cholangiocarcinoma progression through epigenetic augmentation of TMED2 and PARD3B mRNA stabilization. In Journal of gastroenterology, 58, 925-944. doi:10.1007/s00535-023-02015-5. https://pubmed.ncbi.nlm.nih.gov/37391589/

6. Xu, Yongfang, Chen, Yunhao, Yao, Yinan, Cheng, Jun, Zhou, Jianying. 2021. VIRMA contributes to non-small cell lung cancer progression via N6-methyladenosine-dependent DAPK3 post-transcriptional modification. In Cancer letters, 522, 142-154. doi:10.1016/j.canlet.2021.08.027. https://pubmed.ncbi.nlm.nih.gov/34520821/