Tight Junction Protein 1 Suppresses Kidney Renal Clear Cell Carcinoma Cells Proliferation by Inducing Autophagy

被引:1
|
作者
Li, Miao [1 ,3 ,4 ]
Zhou, Di-Sheng [1 ]
Shao, Xin-Rong [1 ]
Chan, Sze-Hoi [1 ]
Dong, Zhao-Xia [1 ]
Liu, Xue-Qi [1 ]
Chen, Shu-Na [1 ]
Qi, Lin [1 ]
Zarate, Luis Velasquez [2 ]
Wang, Xiao-Mei [3 ,4 ]
Du, Xin [3 ,4 ]
Zhang, Xing-Ding [1 ]
机构
[1] Sun Yat Sen Univ, Shenzhen Key Lab Syst Med Inflammatory Dis, Sch Med, Affiliated Hosp 7, Shenzhen Campus, Shenzhen, Peoples R China
[2] Augusta Univ, Med Coll Georgia, Augusta, GA 30912 USA
[3] Shenzhen Univ, Dept Hematol, Affiliated Hosp 1, Shenzhen Peoples Hosp 2,Guangdong Key Lab Biomed M, Shenzhen 518060, Peoples R China
[4] Shenzhen Univ, Shenzhen Bone Marrow Transplantat Publ Serv Platfo, Affiliated Hosp 1, Shenzhen Peoples Hosp 2,Guangdong Key Lab Biomed M, Shenzhen 518060, Peoples R China
来源
基金
中国国家自然科学基金;
关键词
KIRC; Tight junction protein 1; autophagy; proliferation; BREAST-CANCER; GENE; BECLIN-1; CONTRIBUTES; EXPRESSION; TUMORIGENESIS; TEMSIROLIMUS; INHIBITION; APOPTOSIS; MOTILITY;
D O I
10.7150/ijms.81065
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:1448 / 1459
页数:12
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