No small matter: microRNAs - key regulators of cancer stem cells.
No small matter: microRNAs - key regulators of cancer stem cells.
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发表时间：
2010-02
影响因子：
0.1
通讯作者：
Qing Ji;D. Karnak;P. Hao;Rong-quan Wang;Liang Xu
中科院分区：
文献类型：
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作者：
Qing Ji;D. Karnak;P. Hao;Rong-quan Wang;Liang Xu
新出现的证据表明，肿瘤抑制和致癌miRNAs通过负调节干细胞中某些关键基因的表达，在干细胞自我更新和分化中发挥重要作用。它们也可能是癌症干细胞的关键参与者，这似乎是合乎逻辑的。虽然小的尺寸，miRNAs在癌症干细胞的表观遗传调控中发挥关键作用。具体而言，致癌与肿瘤抑制miRNA的不平衡可能导致癌症干细胞的失调，从而导致癌症干细胞的过度自我更新和存活，以及对化疗/放疗的抗性。我们假设，恢复miRNA的平衡将通过直接和同时调节参与癌症干细胞自我更新和/或分化的下游干细胞通路来纠正这种失调。关键调控通路的恢复可以改善治疗反应。恢复肿瘤抑制miRNA和/或抑制致癌miRNA可能为人类癌症提供新的分子治疗，可能通过调节癌症干细胞。
Emerging evidence demonstrates that both tumor suppressor and oncogenic miRNAs play an essential role in stem cell self-renewal and differentiation by negatively regulating the expression of certain key genes in stem cells. It seems logical that they may also be critical players in cancer stem cells. Though small in size, miRNAs play a key role in the epigenetic regulation of cancer stem cells. Specifically, the imbalance of oncogenic vs. tumor suppressor miRNAs may lead to dysregulation of cancer stem cells, thus causing excessive self-renewal and survival of cancer stem cells, and resistance to chemo/radiotherapy. We postulate that restoring the balance of miRNAs will correct this dysregulation via the direct and simultaneous modulation of downstream stem cell pathways involved in cancer stem cell self-renewal and/or differentiation. The resultant restoration of key regulatory pathways could improve therapeutic response. Restoring tumor suppressor miRNAs and/or inhibiting oncogenic miRNAs may provide a novel molecular therapy for human cancers, potentially via modulating cancer stem cells.