Long Noncoding RNA lnc-TSSK2-8 Activates Canonical Wnt/β-Catenin Signaling Through Small Heat Shock Proteins HSPA6 and CRYAB.
Long Noncoding RNA lnc-TSSK2-8 Activates Canonical Wnt/β-Catenin Signaling Through Small Heat Shock Proteins HSPA6 and CRYAB.
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长非编码 RNA lnc-TSSK2-8 通过小热休克蛋白 HSPA6 和 CRYAB 激活经典 Wnt/β-Catenin 信号传导
DOI：
10.3389/fcell.2021.660576
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发表时间：
2021
影响因子：
5.5
通讯作者：
Wang B
中科院分区：
文献类型：
--
作者：
Fa J;Zhang X;Zhang X;Qi M;Zhang X;Fu Q;Xu Z;Gao Y;Wang B
先天性心脏病（CHD）是全世界最常见的出生缺陷。 22q11.2 缺失综合征是最常见的微缺失疾病，经常与圆锥干畸形相关。目前，剂量敏感基因TBX1已被确定为导致22q11.2缺失的主要致病基因，该基因在心脏流出道发育中受经典Wnt/β-catenin信号通路的调控。在这里，我们报道了长非编码RNA（lncRNA）lnc-TSSK2-8，它包含在22q11.2区域中，它可以通过保护β-连环蛋白免于降解（这可能是由于泛素化减少而导致）来激活典型的Wnt/β-连环蛋白信号传导。这种效应是由两种短热休克蛋白 HSPA6 和 α-β-晶状体蛋白 (CRYAB) 介导的，其表达由 lnc-TSSK2-8 通过竞争性内源 RNA (ceRNA) 机制调节。在临床实践中，拷贝数变异（CNV）的发病机制始终归因于蛋白质编码基因的单倍体不足。在这里，我们报告 22q11.2 lncRNA lnc-TSSK2-8 显着激活了经典的 Wnt/β-catenin 信号传导，该信号在心脏流出道发育中起重要作用，并且应该在 TBX1 的上游发挥作用。我们的结果表明，lncRNA 应该有助于 CNV 相关 CHD 的病因学。
Congenital heart defects (CHDs) are the most common birth defects worldwide. 22q11.2 deletion syndrome is the most common microdeletion disorder that has been frequently associated with conotruncal malformations. By now, the dosage-sensitive gene TBX1 has been adopted as the major pathogenic gene responsible for 22q11.2 deletion, which is regulated by canonical Wnt/β-catenin signaling pathway in heart outflow tract development. Here, we report the long noncoding RNA (lncRNA) lnc-TSSK2-8, which is encompassed in the 22q11.2 region, that can activate canonical Wnt/β-catenin signaling by protecting β-catenin from degradation, which could result from decreased ubiquitination. Such effects were mediated by two short heat shock proteins HSPA6 and α-β-crystallin (CRYAB), whose expression was regulated by lnc-TSSK2-8 through a competing endogenous RNA (ceRNA) mechanism. In clinical practice, the pathogenesis of copy number variation (CNV) was always attributed to haploinsufficiency of protein-coding genes. Here, we report that the 22q11.2 lncRNA lnc-TSSK2-8 significantly activated canonical Wnt/β-catenin signaling, which has major roles in cardiac outflow tract development and should act upstream of TBX1. Our results suggested that lncRNAs should contribute to the etiology of CNV-related CHD.
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影响因子：
7.3
作者：
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通讯作者：
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影响因子：
12.3
作者：
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通讯作者：
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DOI：
10.1073/pnas.1013555107
发表时间：
2010-10-26
影响因子：
11.1
作者：
Bousette, Nicolas;Chugh, Shaan;Gramolini, Anthony O.
通讯作者：
Gramolini, Anthony O.