Shi Hua-Qing, Li Xin, Chen Zhou, Dong Shi, Ye Cheng, Hou Shuang, Fan Dong-Ao, Zhang Hui, Zhou Wen-Ce
The Second Clinical Medical School, Lanzhou University, Lanzhou, China.
Department of General Surgery, The Second Hospital of Lanzhou University, Lanzhou, China.
iScience. 2024 Aug 22;27(9):110782. doi: 10.1016/j.isci.2024.110782. eCollection 2024 Sep 20.
Pancreatic cancer (PC) has a really poor prognosis, and we urgently need to delve deeper into its molecular mechanisms. In this study, we found that KRT19 expression was significantly increased in PC tissues and cell lines and it was linked to unfavorable outcomes for patients. Overexpression of KRT19 boosted the proliferation, migration, and invasion of PC cells. Additionally, miR-374b-5p targets KRT19, inhibiting the activation of the Wnt/β-catenin pathway (WBC), which in turn suppresses epithelial-to-mesenchymal transition (EMT) and the progression of PC. Further experiments showed that under hypoxic conditions, HIF1α was positively correlated with KRT19, promoting its expression. The loss of miR-642a-5p and the upregulation of KRT19 induced by hypoxia can significantly favor PC progression. Plus, the increased expression of KRT19 might act as a predictive marker and potential target for PC treatment.
胰腺癌(PC)的预后非常差,我们迫切需要更深入地探究其分子机制。在本研究中,我们发现KRT19在PC组织和细胞系中的表达显著增加,且与患者的不良预后相关。KRT19的过表达促进了PC细胞的增殖、迁移和侵袭。此外,miR-374b-5p靶向KRT19,抑制Wnt/β-连环蛋白通路(WBC)的激活,进而抑制上皮-间质转化(EMT)和PC的进展。进一步实验表明,在缺氧条件下,HIF1α与KRT19呈正相关,促进其表达。缺氧诱导的miR-642a-5p缺失和KRT19上调可显著促进PC进展。此外,KRT19表达增加可能作为PC治疗的预测标志物和潜在靶点。