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https://doi.org/10.3390/cancers13040756
Title: | MiR-582-5p is a tumor suppressor microRNA targeting the Hippo-YAP/TAZ signaling pathway in non-small cell lung cancer | Authors: | Zhu, Bowen Mitheera, V Finch-Edmondson, Megan Lee, Yaelim Wan, Yue Sudol, Marius DasGupta, Ramanuj |
Keywords: | Hippo MiR-582-5p NSCLC (Non-small Cell Lung Cancer) TAZ (Transcriptional co-activator with PDZ-binding motif aka WWTR1) YAP (Yes-associated protein or YAP1) |
Issue Date: | 11-Feb-2021 | Publisher: | MDPI AG | Citation: | Zhu, Bowen, Mitheera, V, Finch-Edmondson, Megan, Lee, Yaelim, Wan, Yue, Sudol, Marius, DasGupta, Ramanuj (2021-02-11). MiR-582-5p is a tumor suppressor microRNA targeting the Hippo-YAP/TAZ signaling pathway in non-small cell lung cancer. Cancers 13 (4) : 1-21. ScholarBank@NUS Repository. https://doi.org/10.3390/cancers13040756 | Rights: | Attribution 4.0 International | Abstract: | The Hippo-YAP/TAZ signaling pathway is an evolutionarily conserved signaling pathway involved in a broad spectrum of biological processes, including tumorigenesis. Whilst aberrant Hippo-YAP/TAZ signaling is frequently reported in various cancers, the genetic alterations of this pathway are relatively rare, suggesting regulation at the post-transcriptional level. MicroRNAs play key role in tumorigenesis by regulating gene expression post-transcriptionally. Amongst the cancer-relevant microRNAs, miR-582-5p suppresses cell growth and tumorigenesis by inhibiting the expression of oncogenes, including AKT3, MAP3K2 and NOTCH1. Given the oncogenic role of YAP/TAZ in solid tumors, we scrutinized the possible interplay between miR- 582-5p and Hippo-YAP/TAZ signaling. Correlation analysis in NSCLC cells revealed a positive relationship between the expression of mature miR-582-5p and the proportion of phosphorylated YAP/TAZ. Intriguingly, YAP/TAZ knockdown reduced the expression of mature miR-582-5p but increased that of primary miR-582. Overexpression of miR-582-5p resulted in increased phosphorylation of YAP/TAZ with a concomitant reduction in cell proliferation and enhanced apoptosis. Mechanistically, we find that miR-582-5p targets actin regulators NCKAP1 and PIP5K1C, which may be responsible for the observed alteration in F-actin, known to modulate YAP/TAZ. We postulate that regulation of the actin cytoskeleton by miR-582-5p may attenuate YAP/TAZ activity. Altogether, this study reveals a novel mechanism of YAP/TAZ regulation by miR-582-5p in a cytoskeleton-dependent manner and suggests a negative feedback loop, highlighting the therapeutic potential of restoring miR-582-5p expression in treating NSCLC. © 2021 by the authors. Licensee MDPI, Basel, Switzerland. | Source Title: | Cancers | URI: | https://scholarbank.nus.edu.sg/handle/10635/233239 | ISSN: | 2072-6694 | DOI: | 10.3390/cancers13040756 | Rights: | Attribution 4.0 International |
Appears in Collections: | Elements Staff Publications |
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