URI regulates tumorigenicity and chemotherapeutic resistance of multiple myeloma by modulating IL-6 transcription.
URI regulates tumorigenicity and chemotherapeutic resistance of multiple myeloma by modulating IL-6 transcription.
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URI通过调节IL-6转录调节多发性骨髓瘤的致瘤性和化疗耐药性
DOI：
10.1038/cddis.2014.93
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发表时间：
2014-03-13
影响因子：
9
通讯作者：
中科院分区：
文献类型：
--
作者：
在实体肿瘤中充当癌蛋白的非常规蛋白RPB5相互作用（URI）与RNA聚合酶II亚基5相关。但是，它对多发性骨髓瘤（MM）的影响尚未确定在这里与Plasma细胞相比，我们在这里表现出URI在这里的较高范围。使用慢病毒的shRNA，我们建立了稳定的URI敲低MM细胞系，与对照细胞相比，MM细胞的增殖显着减弱，并增加了菌落形成。灵敏度MM朝向硼替佐米。
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 is overexpressed in MM compared with plasma cells derived from healthy volunteers. Side population (SP) cells sorted from MM cells showed a much higher level of URI than non-SP cells. Using lentivirus-delivered shRNA, we established stable URI knockdown MM cell lines. URI inhibition significantly attenuated the proliferation of MM cells and decreased colony formation compared with the control cells. Tumor growth assays in NOD/SCID mice further confirmed the promotion role of URI during MM development in vivo. Furthermore, URI knockdown markedly reduced the abundance of SP in MM cell lines and enhanced the chemotherapeutic sensitivity of MM towards bortezomib. Mechanically, URI appears to be critically involved in modulating STAT3 activity through regulating interleukin (IL)-6 transcription via interaction with NFκBp65. In conclusion, URI may have an important role in the development of MM and chemotherapeutic resistance through activating the IL-6/STAT3 pathway.
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影响因子：
20.3
作者：
Bharti, AC;Shishodia, S;Aggarwal, BB
通讯作者：
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影响因子：
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DOI：
10.1073/pnas.84.24.9035
发表时间：
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影响因子：
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