Han Zhenyuan, Yang Biao, Wang Qin, Hu Yuhua, Wu Yuqiong, Tian Zhen
Department of Oral Pathology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
National Clinical Research Center for Oral Diseases, Shanghai, 200011, China.
Cancer Cell Int. 2021 Mar 2;21(1):142. doi: 10.1186/s12935-021-01839-6.
Invasive malignant pleomorphic adenoma (IMPA) is a highly invasive parotid gland tumor and lacks effective therapy. N6-Methyladenosine (mA) is the most prevalent post-transcriptional modification of mRNAs in eukaryotes and plays an important role in the pathogenesis of multiple tumors. However, the significance of mA-modified mRNAs in IMPA has not been elucidated to date. Hence, in this study, we attempted to profile the effect of IMPA in terms of mA methylation in mRNA.
Methylated RNA immunoprecipitation with next-generation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq) were utilized to acquire the first transcriptome-wide profiling of the mA methylome map in IMPA followed by bioinformatics analysis.
In this study, we obtained mA methylation maps of IMPA samples and normal adjacent tissues through MeRIP-seq. In total, 25,490 mA peaks associated with 13,735 genes were detected in the IMPA group, whereas 33,930 mA peaks associated with 18,063 genes were detected in the control group. Peaks were primarily enriched within coding regions and near stop codons with AAACC and GGAC motifs. Moreover, functional enrichment analysis demonstrated that mA-containing genes were significantly enriched in cancer and metabolism relevant pathways. Furthermore, we identified a relationship between the mA methylome and the RNA transcriptome, indicating a mechanism by which mA modulates gene expression.
Our study is the first to provide comprehensive and transcriptome-wide profiles to determine the potential roles played by mA methylation in IMPA. These results may open new avenues for in-depth research elucidating the mA topology of IMPA and the molecular mechanisms governing the formation and progression of IMPA.
侵袭性恶性多形性腺瘤（IMPA）是一种具有高度侵袭性的腮腺肿瘤，且缺乏有效的治疗方法。N6-甲基腺苷（m⁶A）是真核生物中mRNA最普遍的转录后修饰，在多种肿瘤的发病机制中起重要作用。然而，迄今为止，m⁶A修饰的mRNA在IMPA中的意义尚未阐明。因此，在本研究中，我们试图从mRNA的m⁶A甲基化方面剖析IMPA的影响。
采用甲基化RNA免疫沉淀结合二代测序（MeRIP-seq）和RNA测序（RNA-seq）技术，对IMPA进行首次全转录组范围的m⁶A甲基化图谱分析，随后进行生物信息学分析。
在本研究中，我们通过MeRIP-seq获得了IMPA样本和癌旁正常组织的m⁶A甲基化图谱。在IMPA组中，共检测到与13735个基因相关的25490个m⁶A峰，而在对照组中检测到与18063个基因相关的33930个m⁶A峰。峰主要富集在编码区和终止密码子附近，具有AAACC和GGAC基序。此外，功能富集分析表明，含m⁶A的基因在癌症和代谢相关途径中显著富集。此外，我们确定了m⁶A甲基化组与RNA转录组之间的关系，表明m⁶A调节基因表达的机制。
我们的研究首次提供了全面的全转录组图谱，以确定m⁶A甲基化在IMPA中发挥的潜在作用。这些结果可能为深入研究IMPA的m⁶A拓扑结构以及控制IMPA形成和进展的分子机制开辟新途径。
