Shenzhen Key Laboratory for Systems Medicine in Inflammatory Diseases, School of Medicine, Shenzhen Campus of Sun Yat-Sen University, The Seventh Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Shenzhen, China.
Department of Hematology and Shenzhen Bone Marrow Transplantation Public Service Platform, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen University, Shenzhen 518060, China.
Int J Med Sci. 2023 Sep 11;20(11):1448-1459. doi: 10.7150/ijms.81065. eCollection 2023.
TJP1, an adaptor protein of the adhesive barrier, has been found to exhibit distinct oncogenic or tumor suppressor functions in a cell-type dependent manner. However, the role of TJP1 in kidney renal clear cell carcinoma (KIRC) remains to be explored. The results showed a marked down-regulation of TJP1 in KIRC tissues compared to normal tissues. Low expression of TJP1 was significantly associated with high grade and poor prognosis in KIRC. Autophagosome aggregation and LC3 II conversion demonstrated that TJP1 may induce autophagy signaling in 786-O and OS-RC-2 cells. Knockdown of TJP1 led to a decrease in the expression of autophagy-related genes, such as BECN1, ATG3, and ATG7. Consistently, TJP1 expression showed a significant positive correlation with these autophagy-related genes in KIRC patients. Furthermore, the overall survival analysis of KIRC patients based on the expression of autophagy-related genes revealed that most of these genes were associated with a good prognosis. TJP1 overexpression significantly suppressed cell proliferation and tumor growth in 786-O cells, whereas the addition of an autophagy inhibitor diminished its inhibitory function. Taken together, these results suggest that TJP1 serves as a favorable prognostic marker and induces autophagy to suppress cell proliferation and tumor growth in KIRC.
紧密连接蛋白 1（TJP1）作为黏附连接的衔接蛋白，其在依赖于细胞类型的方式下表现出明显的致癌或肿瘤抑制功能。然而，TJP1 在肾透明细胞癌（KIRC）中的作用仍有待探索。结果表明，与正常组织相比，KIRC 组织中 TJP1 的表达明显下调。TJP1 的低表达与 KIRC 的高级别和预后不良显著相关。自噬体聚集和 LC3 II 转化表明，TJP1 可能在 786-O 和 OS-RC-2 细胞中诱导自噬信号。TJP1 的敲低导致自噬相关基因（如 BECN1、ATG3 和 ATG7）的表达减少。一致地，TJP1 的表达与 KIRC 患者中的这些自噬相关基因呈显著正相关。此外，基于自噬相关基因表达的 KIRC 患者的总生存分析显示，这些基因中的大多数与良好的预后相关。TJP1 的过表达显著抑制了 786-O 细胞的增殖和肿瘤生长，而自噬抑制剂的添加则减弱了其抑制功能。综上所述，这些结果表明 TJP1 作为一个有利的预后标志物，通过诱导自噬来抑制 KIRC 中的细胞增殖和肿瘤生长。
