TERC promotes non-small cell lung cancer progression by facilitating the nuclear localization of TERT

被引:2
|
作者
Sun, Haohui [1 ,4 ]
Li, Xiaodi [1 ,4 ]
Long, Qian [1 ,2 ,4 ]
Wang, Xiaonan [1 ]
Zhu, Wancui [1 ]
Chen, Enni [1 ]
Zhou, Wenhao [1 ]
Yang, Han [1 ]
Huang, Chuyang [3 ]
Deng, Wuguo [1 ]
Chen, Miao [1 ]
机构
[1] Sun Yat Sen Univ, Canc Ctr, State Key Lab Oncol South China, Guangzhou 510060, Guangdong, Peoples R China
[2] Sun Yat Sen Univ, Collaborat Innovat Ctr Canc Med, Canc Ctr, Guangzhou 510060, Guangdong, Peoples R China
[3] Cent South Univ, Xiangya Hosp 2, Dept Gen Surg, Changsha 410011, Hunan, Peoples R China
[4] Univ South China, Shaoyang Cent Hosp, Dept Urol, Shaoyang 422000, Hunan, Peoples R China
基金
中国国家自然科学基金;
关键词
TELOMERASE REVERSE-TRANSCRIPTASE; RNA COMPONENT; DNA METHYLATION; GENE; INHIBITION; HTERT; TRAFFICKING; ASSOCIATION; RECRUITMENT; BIOGENESIS;
D O I
10.1016/j.isci.2024.109869
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The core of telomerase consists of the protein subunit telomerase reverse transcriptase (TERT) and the telomerase RNA component (TERC). So far, the role of TERC in cancer development has remained elusive. Here, we found TERC expression elevated in non -small cell lung cancer (NSCLC) tissues, which was associated with disease progression and poor prognosis in patients. Using NSCLC cell lines and xenograft models, we showed that knockdown of TERC caused cell cycle arrest, and inhibition of cell proliferation and migration. Mechanistically, TERC was exported to the cytoplasm by nuclear RNA export factor 1 (NXF1), where it mediated the interaction of TERT with other telomerase subunits. Depletion of TERC hindered the assembly and subsequent nuclear localization of the telomerase complex, preventing TERT from functioning in telomere maintenance and transcription regulation. Our findings suggest that TERC is a potential biomarker for NSCLC diagnosis and prognosis and can be a target for NSCLC treatment.
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页数:21
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