miR-136 modulates TGF-β1-induced proliferation arrest by targeting PPP2R2A in keratinocytes.
miR-136 modulates TGF-β1-induced proliferation arrest by targeting PPP2R2A in keratinocytes.
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miR-136 通过靶向角质形成细胞中的 PPP2R2A 调节 TGF-β1 诱导的增殖抑制
DOI：
10.1155/2015/453518
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发表时间：
2015
影响因子：
--
通讯作者：
Pang X
中科院分区：
文献类型：
--
作者：
Zhang D;Wang J;Wang Z;Zhang T;Shi P;Wang X;Zhao F;Liu X;Lin X;Pang X
角质形成细胞的增殖对于伤口的愈合能力至关重要，越来越多的证据证明microRNA的失调参与角质形成细胞的增殖。然而，其分子机制仍有待完全阐明。在此，我们发现，HaCaT细胞和正常人表皮角质形成细胞（NHEK）中的miR-136在TGF-β1处理后显著降低，并且是Smad 3依赖性方式。通过细胞增殖试验和细胞周期分析，我们发现通过转染重新引入miR-136以及PPP 2 R2 A沉默，抵消了TGF-β诱导的HaCaT细胞增殖停滞。此外，PPP 2 R2 A通过双荧光素酶报告基因测定和蛋白质印迹法被验证为miR-136的直接靶标。这些数据表明，miR-136可能通过靶向角质形成细胞中的PPP 2 R2 A，在TGF-β1诱导的增殖抑制过程中发挥重要作用，这可能是改善皮肤伤口愈合的潜在靶点。
Keratinocytes proliferation is critical for the capacity to heal wounds and accumulating evidences have proved that dysregulation of microRNAs is involved in proliferation of keratinocytes. However, the molecular mechanisms remain to be completely elucidated. Here, we show that miR-136 was significantly decreased by TGF-β1 treatment in HaCaT cells and normal human epidermal keratinocytes (NHEK), and it was a Smad3-dependent manner. By cell proliferation assay and cell cycle analysis, we found that reintroduction of miR-136 by transfection, as well as PPP2R2A silencing, counteracted TGF-β-induced proliferation arrest in HaCaT cells. Further, PPP2R2A was verified as a direct target of miR-136 by dual-luciferase reporter assays and Western blotting. These data suggest that miR-136 may play an important role during TGF-β1-induced proliferation arrest by targeting PPP2R2A in keratinocytes, which might represent a potential target for improving skin wound healing.
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影响因子：
4.6
作者：
Rasanen, Kati;Vaheri, Antti
通讯作者：
Vaheri, Antti
影响因子：
9
作者：
Viticchie, G.;Lena, A. M.;Cianfarani, F.;Odorisio, T.;Annicchiarico-Petruzzelli, M.;Melino, G.;Candi, E.
通讯作者：
Candi, E.
DOI：
10.1073/pnas.1001653107
发表时间：
2010-04-13
影响因子：
11.1
作者：
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通讯作者：
Sen, Chandan K.
影响因子：
4.8
作者：
Overstreet JM;Samarakoon R;Meldrum KK;Higgins PJ
通讯作者：
Higgins PJ
影响因子：
6.5
作者：
Antonini, Dario;Russo, Monia T.;Missero, Caterina
通讯作者：
Missero, Caterina