miR-7977 inhibits the Hippo-YAP signaling pathway in bone marrow mesenchymal stromal cells

• DOI: 10.1371/journal.pone.0213220
• Publication Date: 2019-03-05T19:06:10Z
• Authors: Masahiro Yoshida; Hiroto Horiguchi; Shohei Kikuchi; Satoshi Iyama; Hiroshi Ikeda; Akari Goto; Yutaka Kawano; Kazuyuki Murase; Kohichi Takada; Koji Miyanishi; Junji Kato; Masayoshi Kobune
• Keywords: Hippo signaling pathway; YAP1

We and others have demonstrated that various abnormalities of the bone marrow (BM) mesenchymal stromal cells (MSCs) such as aberrant cytokine expression, abnormal hedgehog signaling, impaired miRNA biogenesis are observed in patients with acute myeloid leukemia (AML). However, underlying mechanisms to induce dysfunction BM MSCs not yet been clarified. previously showed AML release abundant exosomal miR-7977, which, turn, enters (MSCs). precise function miR-7977 is known. In this study, we performed transduction a mimic into MSCs, compared transcriptomes between control-transduced (n = 3) miR-7977-transduced 3), conducted pathway analysis. The array data revealed expression 0.05% genes was reduced 2-fold 0.01% increased 2-fold. Interestingly, approximately half these possessed target site, while other did not, suggesting regulates gene level directly indirectly. Gene set enrichment analysis sets Yes-associated protein 1 (YAP1) _up were significantly enriched (p<0.001, q<0.25), modulates Hippo-YAP signaling pathway. Visualization network Hippo core kinase, STK4. inactivated proven by GFP-tagged YAP nuclear trans localization TEAD reporter assay. MSC cell line, HTS-5, elevated saturation density enhanced entry cycle. These results suggest critical factor BM-MSCs may be involved upregulation leukemia-supporting stroma growth.