端粒酶核酸分子之生理意義及藥物開發

Telomerase RNA as a Target in Drug Development

黃豐淳(Fong-Chun Huang) ； 林敬哲(Jing-Jer Lin)

《化學》 68卷4期 (2010/12) Pp. 271-279

https://doi.org/10.6623/chem.2010026

摘要

端粒長度的維持對細胞維持染色體的完整性、避免染色體末端之間的連結、以及確保染色體的完整複製。正常人類體細胞隨著細胞持續分裂，端粒長度會逐漸縮短，當端粒短至一定程度時會啟動老化機制而使細胞處於停滯狀態，不再持續分裂生長。然而在大部分的癌細胞中、端粒酶的再活化維持了端粒的長度，而使得癌細胞逃脫此複製的限制。因此，端粒酶的活性對癌細胞的持續生長扮演著十分重要的角色。藉由對於端粒酶的瞭解，近年來已經發展出一系列針對端粒酶RNA的抑制劑。本文將介紹端粒酶以及端粒酶RNA的生理作用以及針對端粒酶RNA的藥物開發過程。

關鍵字

端粒 ； 端粒酶 ； 複製性老化 ； 癌症 ； 互補寡核醣核酸 ； 核酸衍生物

並列摘要

Telomere is important for maintaining chromosome integrity, preventing end-to-end fusion of chromosomes, and facilitating complete telomere replication. In normal human cells, telomere length becomes shorter upon each cell division. Progressive shortening of telomeres then triggers cells to enter a non-dividing senescent state. In most of the cancer cells, however, telomerase activation maintains the telomere length and prevents cells from entering senescence. Telomerase plays an important role in supporting continuous proliferation of cancer cells. Through the understanding of telomerase, a series of inhibitors had been developed targeting the RNA component of telomerase. Here we discuss the function of telomerase, telomerase RNA, and focus on the developments of inhibitors targeting telomerase RNA.

並列關鍵字

Telomeres ； Telomerase ； Replication senescence ； Cancer ； Antisense oligonucleotides ； Nucleic acid derivatives