Li Chao, Wang Wei, Zhong Binlong, Zhao Lei, Li Juan, Yu Yihan, Zhang Zhicai, Pu Feifei, Liu Jianxiang
Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China.
Department of Orthopedics, Traditional Chinese and Western Medicine Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China.
Genes Dis. 2024 Nov 30;12(4):101474. doi: 10.1016/j.gendis.2024.101474. eCollection 2025 Jul.
The long non-coding RNA taurine up-regulated gene 1 (TUG1) has been reported to be involved in various cancers, but its role in chondrosarcoma (CHS) remains a mystery. This research aimed to examine the function of TUG1 in CHS. We found that TUG1 expression was elevated in CHS. Functional assays demonstrated that TUG1 had a crucial role in the CHS cell progression. Mechanistically, TUG1 recruited ALYREF to maintain the stabilization of enhancer of zest homolog 2 (EZH2) mRNA and expression of H3K27me3, repressing the transcription of the tumor-suppressor gene . Additionally, exosomal TUG1 enhanced the polarization of M2 tumor-associated macrophages, which increased the proliferation and metastasis of CHS. Taken together, this study revealed the oncogenic role of TUG1 in CHS and its interactions with the downstream regulatory axis, offering novel insights into the tumorigenic mechanism of CHS.
据报道，长链非编码RNA牛磺酸上调基因1（TUG1）与多种癌症有关，但其在软骨肉瘤（CHS）中的作用仍是个谜。本研究旨在探讨TUG1在CHS中的功能。我们发现TUG1在CHS中表达升高。功能分析表明，TUG1在CHS细胞进展中起关键作用。机制上，TUG1招募ALYREF以维持zest同源物2（EZH2）mRNA的稳定性和H3K27me3的表达，从而抑制肿瘤抑制基因的转录。此外，外泌体TUG1增强了M2肿瘤相关巨噬细胞的极化，这增加了CHS的增殖和转移。综上所述，本研究揭示了TUG1在CHS中的致癌作用及其与下游调控轴的相互作用，为CHS的肿瘤发生机制提供了新的见解。
