https://blog.superhyydl.org/tags/trdmt1/Recent content in TRDMT1 on Superhyydl's BlogHugozh-cnSun, 06 Sep 2026 00:00:00 +0000https://blog.superhyydl.org/reading/trdmt1-mediated-mrna-m5c-methylation-decreases-chemotherapy/Sun, 06 Sep 2026 00:00:00 +0000https://blog.superhyydl.org/reading/trdmt1-mediated-mrna-m5c-methylation-decreases-chemotherapy/<h2 id="一句话亮点">一句话亮点</h2> <p>化疗打击下，胰腺癌反手给mRNA戴上&quot;m5C安全帽&quot;——TRDMT1被DNA损伤唤醒，一边给IRS2打上甲基化标记激活生存信号，一边召唤RAD51等HR修复队员，硬生生把化疗的杀伤力扛了过去。</p> <h2 id="背景痛点">背景/痛点</h2> <p>胰腺导管腺癌（PDAC）是公认的&quot;癌王&quot;，化疗（GEM、5-FU、奥沙利铂、伊立替康等）至今仍是基石方案，但耐药问题让疗效像一拳打在棉花上。</p> <p>目前关于PDAC化疗耐药的研究，大多盯着DNA层面的修复或基因组突变。但作者团队之前发现了一个有意思的现象：mRNA上的m5C甲基化像一种&quot;损伤代码&quot;，可能在DNA损伤部位发挥作用。不过，这个修饰在胰腺癌里到底谁在管？影响了下游哪些通路？是不是真的跟化疗耐药挂钩？这些都还是问号。</p> <p><img alt="Fig. 1：Global profiling of mRNA m5C methylation and transcriptional responses to chemotherapy-induced DNA damage in pancreatic cancer cells (a) Schematic of the dot blot–based workflow for global quantification of mRNA m5C. (b) Dot blot of mRNA m5C in Mia PaCa-2 and AsPC-1 cells treated with gemcitabine (GEM) or 5-fluorouracil (5-FU). (c) Total RNA m5C levels in pancreatic cancer cells following GEM or 5-FU treatment. (d) Sequence context (±10 bp) surrounding significant m5C sites; all sites (top), GEM-enriched sites (middle), and PBS-enriched sites (bottom). (e) Distribution of hyper- and hypo-methylated m5C sites (GEM vs PBS) across major mRNA regions. (f) Schematic of RNA-seq workflow for GEM-versus PBS-treated pancreatic cancer cells. (g) Expression of repre\u00ad sentative m5C regulatory genes before and after GEM treatment. (h) Volcano plot of differentially expressed genes in GEM-treated cells. (i) Heatmap of selected RNA- modification–related genes following DNA-damaging treatments. (j) Expression of TRDMT1 after H2O2, GEM, or 5-FU treatment. (k) TRDMT1 expression in TCGA pancreatic cancer tumors and adjacent normal tissues. (a) Created in BioRender. Luo, W. (2026) https://BioRender.com/6tvfcmr." loading="lazy" src="https://blog.superhyydl.org/images/reading/trdmt1-mediated-mrna-m5c-methylation-decreases-chemotherapy/figure-01.png"></p>