端粒酶——干扰素抗肿瘤的新靶点

Telomerase—An Anticancer Target of Interferon

端粒酶(telomerase)是一种具有逆转录活性的核糖核蛋白酶.端粒酶的异常活化是细胞永生化和肿瘤形成的关键步骤.端粒酶活性与细胞周期及细胞凋亡调控密切相关;端粒酶由端粒酶逆转录酶、端粒酶RNA、端粒酶相关蛋白质组成,端粒酶逆转录酶是端粒酶活性的决定性组分.干扰素(interferon)是一种具有抗病毒、抗增殖、抗肿瘤和免疫调节等功能的细胞因子;近年研究表明,干扰素通过相关信号转导途径而调节端粒酶活性,诱导细胞凋亡,为肿瘤的生物治疗提供了新思路;但干扰素与端粒酶活性相关的抗肿瘤机制研究尚不充分.本文综述干扰素通过调节端粒酶逆转录酶转录因子的表达和相互作用而抑制端粒酶活性、调节细胞周期并诱导细胞凋亡等抗肿瘤作用机制.

Telomerase is a ribonucleoprotein with a reverse transcriptase activity, which is related to the regulation of cell cycle and apoptosis. Human telomerase is composed of a key component of reverse transcriptase that complex with telomerasc RNAs and telomerase-associated proteins. Abnormal activation of telomerase is a significant event associated with cell immortalization and malignant transformation. Interferon is a multifunctional cytokine with powerful antiviral, antiproliferation, anticancer and immunomodulatory effects. Recent studies have shown that interferon regulated telomerase activity and induces apoptosis, suggesting that the related signaling pathways could be a new target of cancer therapy. This review discusses the possible anti-tumor mechanisms of interferon, including the inhibition of telomerase activity, regulation of cell cycle, induction of apoptosis, and interaction with transcription factors for telomerase reverse transcriptase biosynthesis.