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Che-1/miR-590-3p/TAZ axis sustains multiple myeloma disease

ABSTRACT: Multiple myeloma (MM) is a blood disease characterized by the malignant accumulation of monoclonal plasma cells in the bone marrow. Among the pathological consequences of the MM, defects in osteogenesis characterized by osteolytic lesions, osteopenia, and pathologic fractures are frequently described. Che-1/AATF (Che-1) is a co-transcriptional factor involved in MM transformation and proliferation. Here, we show that Che-1 expression in MM contributes to maintaining low level of WWTR1 (TAZ), a transcriptional coactivator downstream of the Hippo-signaling pathway. We report that the miR-590-3p, deriving from the mRNA splicing of the EIF4H host gene, can target TAZ, contributing to downregulating its expression in MM. Furthermore, we demonstrate by in vivo and in vitro experiments that Che-1 transcriptionally induces EIF4H gene. We provide data to support that miR-590-3p is secreted by MM cells in vitro and in vivo and that can inhibit TAZ levels and the physiological transcriptional expression of osteogenic-related genes, in mesenchymal stem cells. Our findings unveil an unexplored novel Che-1/miR-590-3p/TAZ axis in MM tumorigenesis by providing a rationale to explore the therapeutic potential of metastatic bone lesions.

ORGANISM(S): Homo sapiens

PROVIDER: GSE234642 | GEO | 2024/04/10

REPOSITORIES: GEO

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Che-1/miR-590-3p/TAZ axis sustains multiple myeloma disease

Project description:Che-1/miR-590-3p/TAZ axis sustains multiple myeloma disease

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Che-1/AATF sustains cell growth and global transcription in Multiple Myeloma through the maintenance of open chromatin structure [RNA-Seq]

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Transcript expression levels of neonatal mouse cardiomyocytes mock-transfected, or transfected with cel-miR-67, hsa-miR-590-3p or hsa-miR-199a-3p

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AATF interactome in human Kms27 cells

Project description:Multiple myeloma is a hematological neoplasm of plasma cells characterized by an abnormal production of immunoglobulins. Che-1/AATF (Che-1) is an RNA binding protein involved in transcription regulation and highly expressed in this malignancy. In order to better characterize its functions in this type of disease, we performed co-immunoprecipitation experiments coupled with a mass-spec analysis by using total MM Kms27 cell lysates. From this analysis we were able to identify more than 600 proteins significantly enriched in Che-1 precipitates. As expected from its role in ribosomal RNA maturation, the Che-1 interactome contains numerous proteins involved in pre-rRNA processing and several ribosomal proteins. Notably, among other proteins interacting with Che-1, we identified many essential components of the paraspeckle which play an important role in the regulation of gene expression.

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