人端粒酶逆转录酶肿瘤相关反馈调节机制的研究进展

Research progress in the feedback regulation of telomerase reverse transcriptase related in cancer

人端粒酶逆转录酶(human telomerase reverse transcriptase,h TERT)是端粒酶的催化亚单位,尤其是端粒酶活性的限速因子,大量转录因子参与h TERT的调节。h TERT在超过90%的肿瘤中表达,对肿瘤细胞的持续增殖发挥着重要作用。此外,h TERT能调节诸如细胞周期调控、细胞信号转导等不同细胞生物学过程中众多基因的表达。因此,h TERT在肿瘤中既是效应因子又是调节因子。然而,h TERT与其靶基因之间的相互作用机制还尚未完全明确。本综述重点关注不同的信号转导通路和基因参与h TERT的反馈调节及其机制,进一步认识端粒酶的非端粒延长功能,从而可能成为肿瘤治疗潜在的新靶点。

Telomerase reverse transcriptase （ TERT） is the catalytic component of telomerase, especially the rate limiting determinant of telomerase activity.A comprehensive network of transcription factors has been shown to be involved in the regulation of TERT.TERT has been reported to be over-expressed in more than 90%of cancers, thereby playing a criti-cal role in sustained proliferation and survival potentials of various cancer cells.Furthermore, accumulating evidence has suggested that TERT could modulate the expression of numerous genes involved in diverse group of cellular processes, in-cluding cell cycle regulation and cellular signaling.Therefore, it indicates that TERT is both an effector and a regulator in carcinoma.However, the mechanisms of the interaction between TERT and its target genes are still not fully understood.In this review, we focus on various signaling pathways and genes that participate in the feedback regulation of TERT and the underlying feedback regulation mechanism of TERT, to further provide new insights into non-telomeric functions of telom-erase and potentially novel therapeutic target for cancer.