Cell-Cycle-Targeting MicroRNAs as Therapeutic Tools against Refractory Cancers

Abstract

SUMMARY Cyclins and cyclin-dependent kinases (CDKs) are hyperactivated in numerous tumors. To identify means of interfering with cyclins/CDKs, we performed nine genome-wide screens for human microRNAs (miRNAs) directly regulating cell cycle proteins. We uncovered a distinct class of miRNAs that target nearly all cyclins/CDKs, which are very effective in inhibiting cancer cell proliferation. By profiling the response of over 120 human cancer cell lines, we derived an expression-based algorithm that can predict the response of primary tumors to cell cycle-targeting miRNAs. Using systemic administration of nanoparticle-formulated miRNAs, we inhibited tumor progression in seven mouse xenograft models, including three treatment-refractory patient-derived tumors, without affecting normal tissues. Our results highlight the utility of using cell cycle-targeting miRNAs for treatment of refractory cancer types.

Cell‐to‐cell communication: microRNAs as hormones

“…After discovering the role of miRNAs in cell–cell signaling and TME, targeting miRNAs as anticancer therapeutic strategy is becoming more realistic and promising. Several groups designed miRNA overexpression or inhibition systems as a therapeutic strategy, and this approach led to promising outcomes in vivo (Bayraktar et al ., 2017; Hydbring et al ., 2017; Mangala et al ., 2016). For instance, Mangala et al .…”

Not So Fast: Cultivating miRs as Kinks in the Chain of the Cell Cycle

“…The study by Hydbring et al brings understanding to the role of miRNAs in controlling cell-cycle regulatory proteins and supports the concept that miRNA function could be harnessed as a means to counteract unchecked cell-cycle progression (summarized in Figure 1) (Hydbring et al, 2017). miRNAs are short, regulatory RNA species that reduce the expression of gene products by inducing mRNA degradation or inhibition of translation (Lagos-Quintana et al, 2001).…”

MicroRNA‐296‐5p promotes healing of diabetic wound by targeting sodium‐glucose transporter 2 (SGLT2)

“…miRNAs regulate a variety of human diseases including cancer, diabetes, and asthma . MiRNAs have important functions in tumourigenesis by regulating cell cycle, cell differentiation, and proliferation . MiR‐296‐5p can inhibit the metastasis and epithelial‐mesenchymal transition (EMT) of colorectal cancer by targeting S100A4 .…”

“…11 MiRNAs have important functions in tumourigenesis by regulating cell cycle, cell differentiation, and proliferation. [12][13][14][15] MiR-296-5p can inhibit the metastasis and epithelial-mesenchymal transition (EMT) of colorectal cancer by targeting S100A4. 16 Moreover, miR-296-5p can also promote invasiveness through downregulating nerve growth factor receptor and caspase-8.…”