miRNA on the Battlefield of Cancer: Significance in Cancer Stem Cells, WNT Pathway, and Treatment

CANCERS(2024)

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摘要
Simple Summary The development of cancer proceeds when the intricate dynamics of the cell are destabilized. It is a multifaceted process, and the involvement of one particularly notorious cell type, cancer stem cells, has been increasingly observed. The WNT signaling pathway is a prominently deregulated pathway in cancer stem cells and has been suggested to maintain properties of self-renewal, tumor initiation, metastasis, and chemoresistance in these cells. MicroRNAs (miRNAs) are post-transcriptional gene regulators that can directly influence gene expression in cancer. As miRNAs hold the potential to be either oncogenic or tumor suppressors, they are found to be highly dysregulated in numerous cancers. Understanding the function of miRNAs in the context of cancer stem cells and the WNT signaling pathway may provide new insights into the treatment of cancer, which is a leading cause of death worldwide.Abstract Carcinogenesis is a complex process characterized by intricate changes in organ histology, biochemistry, epigenetics, and genetics. Within this intricate landscape, cancer stem cells (CSCs) have emerged as distinct cell types possessing unique attributes that significantly contribute to the pathogenesis of cancer. The WNT signaling pathway plays a critical role in maintaining somatic stem cell pluripotency. However, in cancer, overexpression of WNT mediators enhances the activity of beta-catenin, resulting in phenomena such as recurrence and unfavorable survival outcomes. Notably, CSCs exhibit heightened WNT signaling compared to bulk cancer cells, providing intriguing insights into their functional characteristics. MicroRNAs (miRNAs), as post-transcriptional gene expression regulators, modulate various physiological processes in numerous diseases including cancer. Upregulation or downregulation of miRNAs can affect the production of pro-oncogenic or anti-oncogenic proteins, influencing cellular processes that maintain tissue homeostasis and promote either apoptosis or differentiation, even in cancer cells. In order to understand the dysregulation of miRNAs, it is essential to examine miRNA biogenesis and any possible alterations at each step. The potential of a miRNA as a biomarker in prognosis, diagnosis, and detection is being assessed using technologies such as next-generation sequencing. Extensive research has explored miRNA expression profiles in cancer, leading to their utilization as diagnostic tools and the development of personalized and targeted cancer therapies. This review delves into the role of miRNAs in carcinogenesis in relation to the WNT signaling pathway along with their potential as druggable compounds.
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cancer stem cells,WNT signaling pathway,microRNA,miRNA therapeutics
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