Li Chenglong, Lu Tailiang, Chen Hongxi, Yu Zhige, Chen Chaowu
Department of Gastrointestinal Surgery, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, 410005, Hunan Province, China.
Sci Rep. 2024 Sep 16;14(1):21570. doi: 10.1038/s41598-024-59575-6.
Heterogeneous nuclear ribonucleoproteins (hnRNPs), a group of proteins that control gene expression, have been implicated in many post-transcriptional processes. SYNCRIP (also known as hnRNP Q), a subtype of hnRNPs, has been reported to be involved in mRNA splicing and translation. In addition, the deregulation of SYNCRIP was found in colorectal cancer (CRC). However, the role of SYNCRIP in regulating CRC growth remains largely unknown. Here, we found that SYNCRIP was highly expressed in colorectal cancer by analyzing TCGA and GEPIA database. Furthermore, we confirmed the expression of SYNCRIP expression in CRC tumor and CRC cell lines. Functionally, SYNCRIP depletion using shRNA in CRC cell lines (SW480 and HCT 116) resulted in increased caspase3/7 activity and decreased cell proliferation, as well as migration. Meanwhile, overexpression of SYNCRIP showed opposite results. Mechanistically, SYNCRIP regulated the expression of DNA methyltransferases (DNMT) 3A, but not DNMT1 or DNMT3B, which affected the expression of tumor suppressor, p16. More importantly, our in vivo experiments showed that SYNCRIP depletion significantly inhibited colorectal tumor growth. Taken all together, our results suggest SYNCRIP as a potent therapeutic target in colorectal cancer.
不均一核核糖核蛋白（hnRNPs）是一组控制基因表达的蛋白质，已被证明参与许多转录后过程。SYNCRIP（也称为hnRNP Q）是hnRNPs的一种亚型，据报道参与mRNA剪接和翻译。此外，在结直肠癌（CRC）中发现SYNCRIP失调。然而，SYNCRIP在调节CRC生长中的作用仍 largely未知。在这里，我们通过分析TCGA和GEPIA数据库发现SYNCRIP在结直肠癌中高表达。此外，我们证实了SYNCRIP在CRC肿瘤和CRC细胞系中的表达。在功能上，在CRC细胞系（SW480和HCT 116）中使用shRNA耗尽SYNCRIP导致caspase3/7活性增加、细胞增殖减少以及迁移减少。同时，SYNCRIP的过表达显示出相反的结果。机制上，SYNCRIP调节DNA甲基转移酶（DNMT）3A的表达，但不调节DNMT1或DNMT3B，这影响了肿瘤抑制因子p16的表达。更重要的是，我们的体内实验表明，SYNCRIP的耗尽显著抑制了结直肠肿瘤的生长。综上所述，我们的结果表明SYNCRIP是结直肠癌中一个有效的治疗靶点。
