摘要
上皮癌症人群占据人类癌症的80~90%。在癌症的发生发展过程中,细胞失去其上皮特征,并获得具有抗化疗的干细胞样间充质功能,这个过程被称为上皮细胞间质转化(EMT),它在肿瘤的发展过程中起着至关重要的作用。由于细胞上皮细胞间质转化时独特的迁移和侵袭特性,控制上皮细胞间质转化(EMT)为治疗癌症提供了新的希望和机遇。近年来,研究表明大量的基因、非编码RNA以及miRNA与上皮细胞间质转化(EMT)及干细胞样特性的获取紧密相关。虽然这些研究取得了很大进展,但引起细胞转化的分子过程仍然尚不明确。本文主要讨论了被正常抑制的LINE-1(L1)反转录转座子的表达如何对上皮细胞间质转化(EMT)和转移过程进行激活。L1很少在分化的干细胞或成体组织中的表达。然而,它的表达几乎存在于所有上皮细胞癌和未分化状态的干细胞中,这表明了L1活性与癌细胞增殖及转移紧密相关。我们对在癌细胞中L1活性以及L1活性对参与细胞增殖、侵袭和转移的基因的调控进行了概述,对L1在let-7家族miRNA(对参与EMT和转移的基因有调节作用)的差异表达的作用进行了讨论。同时总结了L1编码逆转录酶在上皮细胞的可塑性中的作用,结果表明可能存在一个可以逆转EMT和转移相关的癌细胞干细胞样特性的潜在治疗靶点。
关键词: 抗逆转录病毒治疗,肿瘤干细胞,上皮-间质转化,LINE-1,长链非编码RNA,转移,微RNA,反转录转座子,逆转录酶
Current Molecular Medicine
Title:Activation of LINE-1 Retrotransposon Increases the Risk of Epithelial-Mesenchymal Transition and Metastasis in Epithelial Cancer
Volume: 15 Issue: 7
Author(s): D. Rangasamy, N. Lenka, S. Ohms, J.E. Dahlstrom, A.C. Blackburn and P.G. Board
Affiliation:
关键词: 抗逆转录病毒治疗,肿瘤干细胞,上皮-间质转化,LINE-1,长链非编码RNA,转移,微RNA,反转录转座子,逆转录酶
摘要: Epithelial cancers comprise 80-90% of human cancers. During the process of cancer progression, cells lose their epithelial characteristics and acquire stem-like mesenchymal features that are resistant to chemotherapy. This process, termed the epithelial-mesenchymal transition (EMT), plays a critical role in the development of metastases. Because of the unique migratory and invasive properties of cells undergoing the EMT, therapeutic control of the EMT offers great hope and new opportunities for treating cancer. In recent years, a plethora of genes and noncoding RNAs, including miRNAs, have been linked to the EMT and the acquisition of stem cell-like properties. Despite these advances, questions remain unanswered about the molecular processes underlying such a cellular transition. In this article, we discuss how expression of the normally repressed LINE-1 (or L1) retrotransposons activates the process of EMT and the development of metastases. L1 is rarely expressed in differentiated stem cells or adult somatic tissues. However, its expression is widespread in almost all epithelial cancers and in stem cells in their undifferentiated state, suggesting a link between L1 activity and the proliferative and metastatic behaviour of cancer cells. We present an overview of L1 activity in cancer cells including how genes involved in proliferation, invasive and metastasis are modulated by L1 expression. The role of L1 in the differential expression of the let-7 family of miRNAs (that regulate genes involved in the EMT and metastasis) is also discussed. We also summarize recent novel insights into the role of the L1-encoded reverse transcriptase enzyme in epithelial cell plasticity that suggest it might be a potential therapeutic target that could reverse the EMT and the metastasis-associated stem cell-like properties of cancer cells.
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Cite this article as:
D. Rangasamy, N. Lenka, S. Ohms, J.E. Dahlstrom, A.C. Blackburn and P.G. Board , Activation of LINE-1 Retrotransposon Increases the Risk of Epithelial-Mesenchymal Transition and Metastasis in Epithelial Cancer, Current Molecular Medicine 2015; 15 (7) . https://dx.doi.org/10.2174/1566524015666150831130827
DOI https://dx.doi.org/10.2174/1566524015666150831130827 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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