The ufmylation modification of ribosomal protein L10 in the development of pancreatic adenocarcinoma.

The ufmylation modification of ribosomal protein L10 in the development of pancreatic adenocarcinoma.
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DOI:
10.1038/s41419-023-05877-y
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发表时间:
2023-06-07
影响因子:
9
通讯作者:
Chen, Yijun
Chen, Yijun
中科院分区:
生物学1区
文献类型:
--
作者:
Wang, Kun;Chen, Siyu;Wu, Yue;Wang, Yang;Lu, Yousheng;Sun, Yanzi;Chen, Yijun

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胰腺腺癌(PAAD)是恶性肿瘤中死亡率最高的一种。尽管核糖体蛋白L10 (RPL10)与PAAD存在关联,并且之前也有关于RPL26甲基化的报道,但RPL10甲基化与PAAD发展之间的关系仍未被探索。在这里,我们报道了RPL10的甲基化过程的解剖以及RPL10甲基化在PAAD发展中的潜在作用。在胰腺患者组织和细胞系中均证实了RPL10的甲基化,并鉴定和验证了特异性修饰位点。在表型上,RPL10的甲基化显著增加了细胞的增殖和干性,这主要是由于转录因子KLF4的表达增加。此外,对RPL10中ufmy化位点的突变进一步证明了RPL10 ufmy化与细胞增殖和干细胞性的联系。总的来说,本研究揭示了PRL10的甲基化在增强胰腺癌细胞的干性以促进PAAD的发展中起着重要作用。
Pancreatic adenocarcinoma (PAAD) is the most malignant cancer with a high mortality rate. Despite the association of ribosomal protein L10 (RPL10) with PAAD and previous reports on RPL26 ufmylation, the relationship between RPL10 ufmylation and PAAD development remains unexplored. Here, we report the dissection of ufmylating process of RPL10 and potential roles of RPL10 ufmylation in PAAD development. The ufmylation of RPL10 was confirmed in both pancreatic patient tissues and cell lines, and specific modification sites were identified and verified. Phenotypically, RPL10 ufmylation significantly increased cell proliferation and stemness, which is principally resulted from higher expression of transcription factor KLF4. Moreover, the mutagenesis of ufmylation sites in RPL10 further demonstrated the connection of RPL10 ufmylation with cell proliferation and stemness. Collectively, this study reveals that PRL10 ufmylation plays an important role to enhance the stemness of pancreatic cancer cells for PAAD development.
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