Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.
Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.
Am J Pathol. 2019 May;189(5):966-974. doi: 10.1016/j.ajpath.2018.06.025. Epub 2018 Sep 29.
miRNAs are small RNAs that influence gene expression by targeting mRNAs. Depending on the function of their target genes, miRNAs may regulate the expression of oncogenes and tumor suppressors, thereby contributing to the promotion or inhibition of tumor progression. Ductal carcinoma in situ (DCIS), although often diagnosed as breast cancer, is a potential precursor to invasive ductal carcinoma. Many of the genetic events required for the invasive progression of DCIS occur at the preinvasive stage, and these events include changes in the expression of miRNAs. Aberrant expression of miRNAs can influence specific oncogenic or tumor-suppressive pathways required for breast cancer progression. miRNAs in DCIS have been shown to influence hormone signaling, cell-cell adhesion, epithelial-to-mesenchymal transition, transforming growth factor β signaling, maintenance of cancer stem cells, and modulation of the extracellular matrix. Additionally, extracellular DCIS miRNAs, such as those found in exosomes, may promote invasive progression by modifying the tumor microenvironment. Here, we review the miRNAs that have been identified in DCIS and how they may contribute to the progression to invasive disease. We also touch on the current state of miRNA therapy development, including the current challenges, and discuss the key future perspectives for research into miRNA function for the purpose of miRNA therapy development for DCIS.
miRNAs 是一种通过靶向 mRNAs 影响基因表达的小 RNA。根据其靶基因的功能，miRNAs 可能调节癌基因和肿瘤抑制基因的表达，从而促进或抑制肿瘤的进展。导管原位癌 (DCIS) 虽然常被诊断为乳腺癌，但它是浸润性导管癌的潜在前体。DCIS 浸润进展所需的许多遗传事件发生在侵袭前阶段，这些事件包括 miRNA 表达的变化。miRNA 的异常表达会影响乳腺癌进展所需的特定致癌或肿瘤抑制途径。已经证明，DCIS 中的 miRNAs 可以影响激素信号、细胞间黏附、上皮-间充质转化、转化生长因子 β 信号、维持癌症干细胞和调节细胞外基质。此外，细胞外 DCIS miRNAs，如外泌体中的 miRNAs，可能通过改变肿瘤微环境来促进浸润进展。在这里，我们综述了在 DCIS 中发现的 miRNAs 及其如何促进浸润性疾病的进展。我们还介绍了 miRNA 治疗开发的现状，包括当前的挑战，并讨论了 miRNA 功能研究的关键未来展望，旨在为 DCIS 的 miRNA 治疗开发提供依据。
