Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology, Nonakuri, Purba Medinipur, India.
Curr Oncol. 2010 Feb;17(1):70-80. doi: 10.3747/co.v17i1.356.
In recent years, various RNA-based technologies have been under evaluation as potential next-generation cancer therapeutics. Micrornas (miRNAS), known to regulate the cell cycle and development, are deregulated in various cancers. Thus, they might serve as good targets or candidates in an exploration of anticancer therapeutics. One attractive candidate for this purpose is let-7 ("lethal-7"). Let-7 is underexpressed in various cancers, and restoration of its normal expression is found to inhibit cancer growth by targeting various oncogenes and inhibiting key regulators of several mitogenic pathways. In vivo, let-7 administration was found effective against mouse-model lung and breast cancers, and our computational prediction supports the possible effectiveness of let-7 in estrogen receptor (ER)-positive metastatic breast cancer. Data also suggest that let-7 regulates apoptosis and cancer stem cell (CSC) differentiation and can therefore be tested as a potential therapeutic in cancer treatment. However, the exact role of let-7 in cancer is not yet fully understood. There is a need to understand the causative molecular basis of let-7 alterations in cancer and to develop proper delivery systems before proceeding to therapeutic applications. This article attempts to highlight certain critical aspects of let-7's therapeutic potential in cancer.
近年来，各种基于 RNA 的技术已被评估为潜在的下一代癌症治疗方法。已知调节细胞周期和发育的 microRNAs（miRNAs）在各种癌症中失调。因此，它们可能作为探索抗癌治疗的良好靶点或候选物。为此目的，一个有吸引力的候选物是 let-7（“致死-7”）。Let-7 在各种癌症中表达不足，其正常表达的恢复被发现通过靶向各种癌基因和抑制几种有丝分裂途径的关键调节剂来抑制癌症生长。在体内，let-7 的给药被发现对小鼠模型的肺癌和乳腺癌有效，我们的计算预测支持 let-7 在雌激素受体（ER）阳性转移性乳腺癌中的可能有效性。数据还表明，let-7 调节细胞凋亡和癌症干细胞（CSC）分化，因此可以作为癌症治疗的潜在治疗方法进行测试。然而，let-7 在癌症中的确切作用尚不完全清楚。在进行治疗应用之前，有必要了解 let-7 在癌症中的改变的因果分子基础，并开发适当的递药系统。本文试图强调 let-7 在癌症治疗中的潜在治疗的某些关键方面。
