文章：

Circ-GSK3B通过上调GSK3B抑制肺腺癌进展

Circ-GSK3B up-regulates GSK3B to suppress the progression of lung adenocarcinoma 

原文发布日期：2022-07-11 

英文摘要：

GSK3B is the mRNA form of glycogen synthase kinase 3 beta (GSK-3β), which is a critical repressor of Wnt/β-catenin signaling pathway and generally inhibited in cancer cells. Plenty of researches have disclosed that circular RNAs, namely circRNAs exert important functions in the progression of various human malignancies including lung adenocarcinoma (LUAD). Therefore, we attempted to explore whether there existed certain circRNAs that could mediate LUAD development by regulating GSK3B expression and Wnt/β-catenin pathway. In the present research, circ-GSK3B (hsa_circ_0066903) was found to be significantly down-regulated in LUAD tissues and cells and it suppressed the proliferation, migration and stemness of LUAD cells. Furthermore, it was discovered that circ-GSK3B competitively sponged miR-3681-3p and miR-3909 to elevate GSK3B expression. Circ-GSK3B could impair the binding ability of FKBP51 to GSK-3β to inhibit the phosphorylation of GSK-3βS9, resulting in the inactivation of Wnt/β-catenin signaling. In addition, the regulatory effect of circ-GSK3B on LUAD tumorigenesis and cell progression was testified through in vitro and in vivo rescue experiments. In conclusion, circ-GSK3B suppressed LUAD development through up-regulating and activating GSK3B. 

摘要翻译： 

GSK3B是糖原合成酶激酶3β（GSK-3β）的mRNA形式，作为Wnt/β-catenin信号通路的关键抑制因子，通常在癌细胞中处于被抑制状态。大量研究揭示环状RNA（circRNAs）在肺腺癌（LUAD）等多种人类恶性肿瘤进展中发挥重要作用。因此，我们试图探究是否存在某些可通过调控GSK3B表达和Wnt/β-catenin通路介导LUAD发展的circRNAs。本研究发现circ-GSK3B（hsa_circ_0066903）在LUAD组织及细胞中显著下调，并能够抑制LUAD细胞的增殖、迁移和干性特征。进一步研究发现，circ-GSK3B通过竞争性吸附miR-3681-3p和miR-3909来提升GSK3B表达水平。Circ-GSK3B可削弱FKBP51与GSK-3β的结合能力，从而抑制GSK-3βS9位点的磷酸化，导致Wnt/β-catenin信号通路失活。通过体外和体内挽救实验，进一步证实了circ-GSK3B对LUAD肿瘤发生和细胞进程的调控作用。综上所述，circ-GSK3B通过上调和激活GSK3B抑制LUAD的发展。

原文链接：

Circ-GSK3B up-regulates GSK3B to suppress the progression of lung adenocarcinoma