miR-200c regulates IL8 expression by targeting IKBKB: a potential mediator of inflammation in leiomyoma pathogenesis.
miR-200c regulates IL8 expression by targeting IKBKB: a potential mediator of inflammation in leiomyoma pathogenesis.
复制标题
DOI：
10.1371/journal.pone.0095370
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Khorram O
中科院分区：
文献类型：
--
作者：
Chuang TD;Khorram O
我们以前曾报道，与配对的子宫肌层相比，平滑肌瘤表达较低水平的miR-200 c和升高的IL-8。在这里，我们解决了miR-200 c的表达的炎症介质和细胞活力的调节功能，使用平滑肌瘤和配对的子宫肌层和他们的分离的原代平滑肌细胞。我们的研究结果表明，平滑肌瘤细胞（LSMC）中miR-200 c的功能获得或敲低通过直接靶向IKBKB和改变NF-κ B活性来调节IL 8 mRNA和蛋白表达。此外，与匹配的子宫肌层相比，平滑肌瘤表达更高水平的磷酸化IKBKB，而IKBKB mRNA和蛋白水平无显著差异。miR-200 c在LSMC中的功能获得导致IkBα磷酸化和p65核转位减少，从而导致IL 8启动子p65转录活性降低，caspase 3/7活性增加，这在IL 8恢复后是不可逆的。综上所述，我们的研究结果提示NF-κB信号通路是miR-200 c调控功能的靶点，而miR-200 c在平滑肌瘤中通过IL 8等炎症介质的转录调控而低水平表达，部分解释了平滑肌瘤的发生发展。
We have previously reported that leiomyoma expressed lower levels of miR-200c and elevated IL8 as compared to paired myometrium. Here we addressed the regulatory functions of miR-200c on the expression of inflammatory mediators and cellular viability using leiomyomas and paired myometrium and their isolated primary smooth muscle cells. Our results indicated that gain-of function or knockdown of miR-200c in leiomyoma smooth muscle cells (LSMC) regulated IL8 mRNA and protein expression through direct targeting of IKBKB and alteration of NF-kB activity. Additionally, leiomyoma expressed higher levels of phosphorylated IKBKB with no significant difference in the level of IKBKB mRNA and protein as compared to matched myometrium. Gain-of function of miR-200c in LSMC resulted in decreased IkBαphosphorylation and p65 nuclear translocation, which led to decreased p65 transcriptional activity of IL8 promoter, and increased caspase 3/7 activity which was not reversible following IL8 restoration. Collectively, our results suggest that NF-κB signaling pathway is a target of miR-200c regulatory function, and low level of miR-200c expression in leiomyoma by transcriptional regulation of inflammatory mediators such as IL8, in part account for development of leiomyomas.
登录
查看更多内容
影响因子：
3.9
作者：
Chuang TD;Panda H;Luo X;Chegini N
通讯作者：
Chegini N
影响因子：
4.6
作者：
Khanjani S;Terzidou V;Johnson MR;Bennett PR
通讯作者：
Bennett PR
影响因子：
56.9
作者：
Delhase, M;Hayakawa, M;Karin, M
通讯作者：
Karin, M
影响因子：
16.6
作者：
Pecot, Chad V.;Rupaimoole, Rajesha;Yang, Da;Akbani, Rehan;Ivan, Cristina;Lu, Chunhua;Wu, Sherry;Han, Hee-Dong;Shah, Maitri Y.;Rodriguez-Aguayo, Cristian;Bottsford-Miller, Justin;Liu, Yuexin;Kim, Sang Bae;Unruh, Anna;Gonzalez-Villasana, Vianey;Huang, Li;Zand, Behrouz;Moreno-Smith, Myrthala;Mangala, Lingegowda S.;Taylor, Morgan;Dalton, Heather J.;Sehgal, Vasudha;Wen, Yunfei;Kang, Yu;Baggerly, Keith A.;Lee, Ju-Seog;Ram, Prahlad T.;Ravoori, Murali K.;Kundra, Vikas;Zhang, Xinna;Ali-Fehmi, Rouba;Gonzalez-Angulo, Ana-Maria;Massion, Pierre P.;Calin, George A.;Lopez-Berestein, Gabriel;Zhang, Wei;Sood, Anil K.
通讯作者：
Sood, Anil K.
影响因子：
2.9
作者：
Panda, Harekrushna;Pelakh, Leslie;Chegini, Nasser
通讯作者：
Chegini, Nasser