6533b857fe1ef96bd12b4504

RESEARCH PRODUCT

Replacement of miR-155 Elicits Tumor Suppressive Activity and Antagonizes Bortezomib Resistance in Multiple Myeloma

Nicola AmodioCiro BottaDaniele CaraccioloCinzia FedericoMarco RossiPierosandro TagliaferriPierfrancesco TassonePierfrancesco TassoneDomenica RonchettiAntonino NeriMaria Eugenia Gallo CantafioValter AgostiChristoph Driessen

subject

0301 basic medicineCancer Researchlcsh:RC254-282ArticlemiR-155PathogenesismiR-15503 medical and health sciences0302 clinical medicineIn vivomicroRNAmedicineMultiple myelomamiRNAmicroRNABortezomibbusiness.industrybortezomiblcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogensmedicine.diseaseIn vitromultiple myeloma030104 developmental biologyOncologyProteasome030220 oncology & carcinogenesisCancer researchbusinessmedicine.drug

description

Aberrant expression of microRNAs (miRNAs) has been associated to the pathogenesis of multiple myeloma (MM). While miR-155 is considered a therapeutic target in several malignancies, its role in MM is still unclear. The analysis of miR-155 expression indicates its down-regulation in MM patient-derived as compared to healthy plasma cells, thus pointing to a tumor suppressor role in this malignancy. On this finding, we investigated miR-155 replacement as a potential anti-tumor strategy in MM. The miR-155 enforced expression triggered anti-proliferative and pro-apoptotic effects in vitro. Given the lower miR-155 levels in bortezomib-resistant as compared to sensitive MM cells, we analyzed the possible involvement of miR-155 in bortezomib resistance. Importantly, miR-155 replacement enhanced bortezomib anti-tumor activity both in vitro and in vivo in a xenograft model of human MM. In primary MM cells, we observed an inverse correlation between miR-155 and the mRNA encoding the proteasome subunit gene PSM&beta

yearjournalcountryeditionlanguage
2019-02-18Cancers
10.3390/cancers11020236http://dx.doi.org/10.3390/cancers11020236