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The Long Noncoding RNA UCA1 Negatively Regulates Melanogenesis in Melanocytes.
Journal of Investigative Dermatology ( IF 6.5 ) Pub Date : 2019-07-02 , DOI: 10.1016/j.jid.2019.04.029
Shiyao Pei 1 , Jing Chen 1 , Jianyun Lu 1 , Shuanghai Hu 1 , Ling Jiang 1 , Li Lei 2 , Yujie Ouyang 1 , Chuhan Fu 1 , Yufang Ding 1 , Si Li 1 , Liyang Kang 1 , Lihua Huang 3 , Hong Xiang 3 , Rong Xiao 4 , Qinghai Zeng 1 , Jinhua Huang 1
Affiliation  

The long noncoding RNA UCA1 was first discovered in bladder cancer and is known to regulate the proliferation and migration of melanoma. However, its role in melanogenesis is unclear. In this study, we aimed to explore the role and mechanism of UCA1 in melanogenesis. Our findings showed that the expression of UCA1 was negatively correlated with melanin content in melanocytes and pigmented nevus. Overexpression of UCA1 in melanocytes decreased melanin content and the expression of melanogenesis-related genes, whereas knockdown of UCA1 in melanocytes had the opposite effect. High-throughput sequencing revealed that microphthalmia-associated transcription factor (MITF), an important transcription factor affecting melanogenesis, was also negatively correlated with the expression of UCA1. Furthermore, the transcription factor CRE-binding protein (CREB), which promotes MITF expression, was negatively regulated by UCA1. The cAMP/protein kinase A (PKA), extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK) signaling pathways, which are upstream of the CREB/MITF/melanogenesis axis, were activated or inhibited in response to silencing or enhancing UCA1 expression, respectively. In addition, enhanced UCA1 expression downregulates the expression of melanogenesis-related genes induced by UVB in melanocytes. In conclusion, UCA1 may negatively regulate the CREB/MITF/melanogenesis axis through inhibiting the cAMP/PKA, ERK, and JNK signaling pathways in melanocytes. UCA1 may be a potential therapeutic target for the treatment of pigmented skin diseases.

中文翻译:

长的非编码RNA UCA1负调控黑色素细胞中的黑色素生成。

长的非编码RNA UCA1最初在膀胱癌中发现,已知可调节黑素瘤的增殖和迁移。但是,其在黑色素生成中的作用尚不清楚。在这项研究中,我们旨在探讨UCA1在黑色素生成中的作用和机制。我们的发现表明,UCA1的表达与黑色素细胞和色素痣中黑色素的含量呈负相关。黑色素细胞中UCA1的过表达降低了黑色素含量和黑色素生成相关基因的表达,而黑色素细胞中UCA1的敲低则具有相反的作用。高通量测序表明,微眼科相关转录因子(MITF),一种影响黑素生成的重要转录因子,也与UCA1的表达呈负相关。此外,转录因子CRE结合蛋白(CREB)促进MITF表达的细胞受UCA1负调控。在CREB ​​/ MITF /黑色素生成轴上游的cAMP /蛋白激酶A(PKA),细胞外信号调节激酶(ERK)和c-Jun N端激酶(JNK)信号传导途径被激活或抑制对沉默或增强UCA1表达的反应。此外,增强的UCA1表达下调了UVB在黑素细胞中诱导的黑素生成相关基因的表达。总之,UCA1可能通过抑制黑素细胞中的cAMP / PKA,ERK和JNK信号通路来负调节CREB ​​/ MITF /黑素生成轴。UCA1可能是治疗色素性皮肤疾病的潜在治疗靶标。CREB ​​/ MITF /黑色素生成轴上游的细胞外信号调节激酶(ERK)和c-Jun N端激酶(JNK)信号通路分别被激活或抑制,以响应沉默或增强UCA1表达。此外,增强的UCA1表达下调了由UVB诱导的黑素细胞中与黑素生成相关的基因的表达。总之,UCA1可能通过抑制黑素细胞中的cAMP / PKA,ERK和JNK信号通路来负调节CREB ​​/ MITF /黑素生成轴。UCA1可能是治疗色素性皮肤疾病的潜在治疗靶标。CREB ​​/ MITF /黑色素生成轴上游的细胞外信号调节激酶(ERK)和c-Jun N端激酶(JNK)信号通路分别被激活或抑制,以响应沉默或增强UCA1表达。此外,增强的UCA1表达下调了由UVB诱导的黑素细胞中与黑素生成相关的基因的表达。总之,UCA1可能通过抑制黑素细胞中的cAMP / PKA,ERK和JNK信号通路来负调节CREB ​​/ MITF /黑素生成轴。UCA1可能是治疗色素性皮肤疾病的潜在治疗靶标。增强的UCA1表达下调了UVB在黑素细胞中诱导的黑素生成相关基因的表达。总之,UCA1可能通过抑制黑素细胞中的cAMP / PKA,ERK和JNK信号通路来负调节CREB ​​/ MITF /黑素生成轴。UCA1可能是治疗色素性皮肤疾病的潜在治疗靶标。增强的UCA1表达下调了UVB在黑素细胞中诱导的黑素生成相关基因的表达。总之,UCA1可能通过抑制黑素细胞中的cAMP / PKA,ERK和JNK信号通路来负调节CREB ​​/ MITF /黑素生成轴。UCA1可能是治疗色素性皮肤疾病的潜在治疗靶标。
更新日期:2019-12-19
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