Downregulation of MicroRNA-152 contributes to high expression of DKK1 in multiple myeloma

Abstract

Multiple myeloma (MM) induced bone lesion is one of the most crippling characteristics, and the MM secreted Dickkopf-1 (DKK1) has been reported to play important role in this pathologic process. However, the underlying regulation mechanisms involved in DKK1 expression are still unclear. In this study, we validated the expression patterns of microRNA (miR) 15a, 34a, 152, and 223 in MM cells and identified that miR-152 was significantly downregulated in the MM group compared with the non-MM group, and that miR-152 level was negatively correlated with the expression of DKK1 in the MM cells. Mechanistic studies showed that manipulating miR-152 artificially in MM cells led to changes in DKK-1 expression, and miR-152 blocked DKK1 transcriptional activity by binding to the 3 0 UTR of DKK1 mRNA. Importantly, we revealed that MM cells stably expressing miR-152 improved the chemotherapy sensitivity, and counteracted the bone disruption in an intrabone-MM mouse model. Our study contributes better understanding of the regulation mechanism of DKK-1 in MM, and opens up the potential for developing newer therapeutic strategies in the MM treatment.

Membrane‐bound Dickkopf‐1 in Foxp3+ regulatory T cells suppresses T‐cell‐mediated autoimmune colitis

“…Previous studies demonstrated thrombocytes (or platelets) or cancer cells as sources of DKK‐1 upon exposure to external stimuli (e.g. parasites or allergens) or alterations in cancerous cells . Notably, membrane‐bound TGF‐ β is also highly expressed in thrombocytes and Treg cells similar to DKK‐1 .…”

“…parasites or allergens) or alterations in cancerous cells. 18,[27][28][29] Notably, membranebound TGF-b is also highly expressed in thrombocytes and Treg cells similar to DKK-1. 30 Although the biological importance of platelet-derived DKK-1 and Treg cellderived DKK-1 is now being addressed by our studies, how the mammalian immune system has evolved to share expression patterns of these two seemingly important immune regulators such as DKK-1 and TGF-b in thrombocytes and Treg cells awaits further studies.…”

Melatonin restrains angiogenic factors in triple-negative breast cancer by targeting miR-152-3p: In vivo and in vitro studies

“…Moreover, the hypoxia increases the expression of pro-angiogenic factors such as pVHL and HIF-1α, or even control epigenetic mechanisms involving microRNAs (miRNAs) [7]. Recent studies demonstrate that the increase of IGF-IR (Insulin-like growth factor 1 receptor) in angiogenesis might be related to other genes, such as HIF-1α (Hypoxia-Inducible Factor) and VEGF leading to angiogenesis [8,9].…”

MicroRNA-152 inhibits cell proliferation of osteosarcoma by directly targeting Wnt/β-catenin signaling pathway in a DKK1-dependent manner

“…However, in our study, we found that the overexpression of microRNA-152 suppressed DKK1 and decreased Wnt/β-catenin in osteosarcoma, and downregulation of microRNA-152 expression to induced DKK1/Wnt/β-catenin in osteosarcoma. Xu et al showed that microRNA-152 contributes DKK1 expression in multiple myeloma (18). Thus it was shown that microRNA-152 could suppressed DKK1 Wnt/β-catenin in osteosarcoma, which may be an important signaling pathways for treatment of osteosarcoma.…”