URI regulates tumorigenicity and chemotherapeutic resistance of multiple myeloma by modulating IL-6 transcription

• DOI: 10.1038/cddis.2014.93
• Publication Date: 2014-03-13T15:40:52Z
• Authors: J-L Fan; J Zhang; L-W Dong; W-J Fu; J Du; H-G Shi; H Jiang; F Ye; H Xi; C-Y Zhang; J Hou; H-Y Wang
• Keywords: Transcription

Unconventional prefoldin RPB5 interactor (URI), which acts as an oncoprotein in solid tumors, is associated with RNA polymerase II subunit 5. However, its impact on multiple myeloma (MM) has not been determined. We demonstrate here that URI overexpressed MM compared plasma cells derived from healthy volunteers. Side population (SP) sorted showed a much higher level of than non-SP cells. Using lentivirus-delivered shRNA, we established stable knockdown cell lines. inhibition significantly attenuated the proliferation and decreased colony formation control Tumor growth assays NOD/SCID mice further confirmed promotion role during development vivo. Furthermore, markedly reduced abundance SP lines enhanced chemotherapeutic sensitivity towards bortezomib. Mechanically, appears to be critically involved modulating STAT3 activity through regulating interleukin (IL)-6 transcription via interaction NFκBp65. In conclusion, may have important resistance activating IL-6/STAT3 pathway.