LncRNA RP6-65G23.1 accelerates proliferation and inhibits apoptosis via p-ERK1/2/p-AKT signaling pathway on keratinocytes
LncRNA RP6-65G23.1 accelerates proliferation and inhibits apoptosis via p-ERK1/2/p-AKT signaling pathway on keratinocytes
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LncRNA RP6-65G23.1 通过 p-ERK1/2/p-AKT 信号通路加速角质形成细胞增殖并抑制细胞凋亡
DOI：
10.1002/jcb.29685
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发表时间：
2020-02-17
影响因子：
4
通讯作者：
Zheng, Yan
中科院分区：
文献类型：
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作者：
Duan, Qiqi;Wang, Guorong;Zheng, Yan
长链非编码rna （LncRNAs）在肝癌、黑色素瘤和牛皮癣等多种疾病的发生发展中发挥着重要作用。同时，lncRNA-RP6-65G23.1在银屑病中表达上调。然而，lncRNA-RP6-65G23.1的表达是否上调并参与角质形成细胞的增殖和凋亡，以及这些过程的机制尚不清楚。本研究的目的就是要解决这些问题。RP6-65G23.1在m5刺激的角质形成细胞中显著上调，刺激HaCaT细胞增殖，抑制HaCaT细胞凋亡。低表达RP6-65G23.1导致HaCaT细胞生长缺陷和凋亡率升高，而过表达RP6-65G23.1则表现出相反的效果。抗凋亡蛋白Bcl-xl和Bcl2在RP6-65G23.1敲低的细胞中表达降低，而在RP6-65G23.1过表达的细胞中表达升高。此外，RP6-65G23.1缺失减弱了细胞外调节激酶1/2 （ERK1/2）和AKT信号通路的活性，诱导G(1)/ s生长停滞。相反，过表达RP6-65G23.1激活ERK1/2和AKT信号通路，以AKT依赖的方式抑制p21和p27的表达，从而促进G1/S进展。我们的研究结果表明，lncRNA-RP6-65G23.1可能通过p-ERK1/2和p-AKT通路调控角质形成细胞的增殖和凋亡，参与银屑病的发病机制。
Long non-coding RNAs (LncRNAs) play essential roles in the development of various diseases including hepatic carcinoma, melanoma, and psoriasis. Meanwhile, lncRNA-RP6-65G23.1 was upregulated in psoriasis. However, it is still unclear whether lncRNA-RP6-65G23.1 expression is upregulated and contributes to keratinocytes proliferation and apoptosis, and which mechanisms are responsible for these processes. The aims of this study are to address these issues. RP6-65G23.1 was significantly upregulated in M5-stimulated keratinocytes and stimulated the proliferation and inhibited the apoptosis of HaCaT cells. Knockdown of RP6-65G23.1 resulted in defects of growth and increased rates of apoptosis in HaCaT cells, while overexpression of RP6-65G23.1 manifested the opposite effects. Consistently, the expression of antiapoptotic proteins Bcl-xl and Bcl2 were decreased in RP6-65G23.1-knockdown cells but elevated in RP6-65G23.1 overexpression cells. In addition, RP6-65G23.1 depletion blunted the activity of extracellular regulated kinase 1/2 (ERK1/2) and AKT signaling pathways and induced G(1)/S-growth arrest. By contrast, overexpression of RP6-65G23.1 activates the ERK1/2 and AKT signaling pathways and inhibits the expression of p21 and p27 in an AKT-dependent manner leading to promote the G1/S progression. Our results suggested that lncRNA-RP6-65G23.1 would contribute to the pathogenesis of psoriasis by regulating the proliferation and apoptosis of keratinocytes via the p-ERK1/2 and p-AKT pathways.