Li Qiuyan, Yang Yuxia, Lin Xiaocong, Chu Lok Ting, Chen Helian, Chen Linsong, Tang Jinjing, Zeng Tao
Department of Medical Laboratory, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524000, P.R. China.
Institute of Biochemistry and Molecular Biology, Guangdong Medical University, Zhanjiang, Guangdong 524023, P.R. China.
Oncol Rep. 2025 Feb;53(2). doi: 10.3892/or.2025.8864. Epub 2025 Jan 10.
Pancreatic cancer is an aggressive tumor, which is often associated with a poor clinical prognosis and resistance to conventional chemotherapy. Therefore, there is a need to identify new therapeutic markers for pancreatic cancer. Although KIN17 is a highly expressed DNA‑ and RNA‑binding protein in a number of types of human cancer, its role in pancreatic cancer development, especially in relation to progression, is currently unknown. The present study verified the upregulation of KIN17 in pancreatic cancer using The Cancer Genome Atlas and Gene Expression Omnibus databases (GSE15471, GSE71989 and GSE62165), and identified an association between the PI3K/Akt/mTOR pathway and patient prognosis using publicly available datasets (Gene Expression Profiling Interactive Analysis). Immunohistochemistry was performed to determine the association between KIN17 and the pathological features of clinical pancreatic cancer samples. Furthermore, knockdown of KIN17 was shown to inhibit the migration and invasion of pancreatic cancer cells, and to reverse epithelial‑mesenchymal transition in pancreatic cancer cells through downregulation of Vimentin and N‑cadherin, and upregulation of E‑cadherin. Through various cellular experiments, the role of KIIN17 was explored in PI3K/AKT/mTOR activity. KIN17 inhibition was shown to suppress the migration and invasion of pancreatic cancer cells through PI3K/AKT/mTOR‑mediated autophagy. Furthermore, combined with mTOR inhibition, dual inhibition could enhance autophagy, leading to anti‑migratory and anti‑invasion effects in pancreatic cancer. In conclusion, the present study indicated that KIN17 may have a role in carcinogenesis and could serve as a prognostic biomarker of pancreatic cancer, owing to its high expression. In addition, KIN17 may be considered a potential therapeutic target with its knockdown having an inhibitory effect on pancreatic cancer.
胰腺癌是一种侵袭性肿瘤，常伴有较差的临床预后以及对传统化疗的耐药性。因此，需要鉴定胰腺癌新的治疗标志物。尽管KIN17在多种人类癌症中是一种高表达的DNA和RNA结合蛋白，但其在胰腺癌发生发展中的作用，尤其是与进展相关的作用，目前尚不清楚。本研究使用癌症基因组图谱和基因表达综合数据库（GSE15471、GSE71989和GSE62165）验证了KIN17在胰腺癌中的上调，并使用公开可用数据集（基因表达谱交互式分析）确定了PI3K/Akt/mTOR通路与患者预后之间的关联。进行免疫组织化学以确定KIN17与临床胰腺癌样本病理特征之间的关联。此外，KIN17基因敲低显示可抑制胰腺癌细胞的迁移和侵袭，并通过下调波形蛋白和N-钙黏蛋白以及上调E-钙黏蛋白来逆转胰腺癌细胞的上皮-间质转化。通过各种细胞实验，探讨了KIN17在PI3K/AKT/mTOR活性中的作用。KIN17抑制通过PI3K/AKT/mTOR介导的自噬抑制胰腺癌细胞的迁移和侵袭。此外，与mTOR抑制联合使用，双重抑制可增强自噬，从而对胰腺癌产生抗迁移和抗侵袭作用。总之，本研究表明，由于KIN17高表达，其可能在致癌过程中发挥作用，并可作为胰腺癌的预后生物标志物。此外，KIN17可能被视为一个潜在的治疗靶点，其基因敲低对胰腺癌具有抑制作用。
