AUTHOR=Fa Jingjing , Zhang Xiaoqing , Zhang Xiaoping , Qi Ming , Zhang Xingyu , Fu Qihua , Xu Zhuoming , Gao Yunqian , Wang Bo 

TITLE=Long Noncoding RNA lnc-TSSK2-8 Activates Canonical Wnt/β-Catenin Signaling Through Small Heat Shock Proteins HSPA6 and CRYAB

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=Volume 9 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.660576

DOI=10.3389/fcell.2021.660576

ISSN=2296-634X

ABSTRACT=Congenital heart defects (CHD) are the most common birth defects worldwide. 22q11.2 deletion syndrome is the most common microdeletion disorder which 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 lncRNA lnc-TSSK2-8, which is encompassed in the 22q11.2 region, 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 CRYAB, whose expression was regulated by lnc-TSSK2-8 through a competing endogenous RNA ceRNA mechanism. In clinical practice, pathogenesis of CNV was always attributed to haploinsufficiency of protein coding genes. Here we report the 22q11.2 lncRNA lnc-TSSK2-8 significantly activated canonical Wnt/𝛃-catenin signaling, which has major roles in cardiac out flow tract development and should act upstream of TBX1. Our results suggested that lncRNAs should contribute to the etiology of CNV related CHD.