Circular RNA circ-TNPO3 suppresses metastasis of GC by acting as a protein decoy for IGF2BP3 to regulate the expression of MYC and SNAIL.
Circular RNA circ-TNPO3 suppresses metastasis of GC by acting as a protein decoy for IGF2BP3 to regulate the expression of MYC and SNAIL.
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环状RNA circ-TNPO3通过作为IGF2BP3的蛋白诱饵调节MYC和SNAIL的表达来抑制胃癌转移
DOI：
10.1016/j.omtn.2021.08.029
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发表时间：
2021-12-03
期刊：
影响因子：
--
通讯作者：
Xiao B
中科院分区：
文献类型：
--
作者：
Yu T;Ran L;Zhao H;Yin P;Li W;Lin J;Mao H;Cai D;Ma Q;Pan X;Wang X;Wu J;Zeng H;Zhang W;Lu D;Luo P;Zou Q;Xiao B
胃癌是我国最常见的胃肠道恶性肿瘤，肿瘤转移是导致预后不良的主要原因。环状RNA（CircRNA）是一类具有重要调控作用的非编码RNA。然而，circRNA在GC转移中的作用尚未完全阐明。在这里，我们报道了循环转运蛋白3（TNPO 3）在103对GC组织中与匹配的非癌组织相比显著下调。circ-TNPO 3的表达水平与胃癌的分化程度有关，血浆circ-TNPO 3可作为胃癌诊断的生物标志物。在功能上，circ-TNPO 3在体外和体内抑制GC的增殖和迁移。我们进一步验证了circ-TNPO 3与胰岛素样生长因子2结合蛋白3（IGF 2BP 3）蛋白竞争性相互作用，从而削弱了IGF 2BP 3稳定MYC mRNA的作用，抑制了MYC及其靶点SNAIL的表达。综上所述，circ-TNPO 3作为IGF 2BP 3的蛋白诱饵来调节MYC-SNAIL轴，从而抑制GC的增殖和转移。因此，circ-TNPO 3有潜力作为GC的治疗靶点。circ-TNPO 3作为IGF 2BP 3的蛋白诱饵，抑制MYC和SNAIL的表达。在胃癌中，下调的circ-TNPO 3减弱了其与IGF 2BP 3的相互作用，并促进MYC及其靶基因SNAIL的表达，从而导致胃癌转移。
Gastric cancer (GC) continues to be the most common gastrointestinal malignancy in China, and tumor metastases are a major reason for poor prognosis. Circular RNAs (circRNAs) are an intriguing type of noncoding RNAs with important regulatory roles. However, the roles of circRNAs in GC metastasis have not been fully elucidated. Here, we reported that circ-transportin 3 (TNPO3) was significantly downregulated in 103 pairs of GC tissues compared with matched noncancerous tissues. The level of circ-TNPO3 expression correlated with differentiation of GC, and plasma circ-TNPO3 could serve as a potential diagnostic biomarker. Functionally, circ-TNPO3 inhibited proliferation and migration of GC in vitro and in vivo. We further verified that circ-TNPO3 competitively interacted with insulin-like growth factor 2 binding protein 3 (IGF2BP3) protein; thus, the role of IGF2BP3 in stabilizing MYC mRNA was weakened, which inhibited the expression of MYC and its target SNAIL. Taken together, circ-TNPO3 acts as a protein decoy for IGF2BP3 to regulate the MYC-SNAIL axis, thereby suppressing the proliferation and metastasis of GC. Therefore, circ-TNPO3 has the potential to serve as a therapeutic target for GC. circ-TNPO3 acts as a protein decoy for IGF2BP3 to inhibit the expression of MYC and SNAIL. In GC, the downregulated circ-TNPO3 weakens its interaction with IGF2BP3 and promotes the expression of MYC and its target gene SNAIL, thereby resulting in GC metastasis.
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