The RNA binding protein QKI5 suppresses ovarian cancer via downregulating transcriptional coactivator TAZ.

The RNA binding protein QKI5 suppresses ovarian cancer via downregulating transcriptional coactivator TAZ.
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RNA结合蛋白QKI5通过下调转录共激活因子TAZ抑制卵巢癌

DOI:
10.1016/j.omtn.2021.07.012
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发表时间:
2021-12-03
期刊:
Molecular therapy. Nucleic acids
影响因子:
--
通讯作者:
Yi P
Yi P
中科院分区:
其他
文献类型:
--
作者:
Liu T;Yang Y;Xie Z;Luo Q;Yang D;Liu X;Zhao H;Wei Q;Liu Y;Li L;Wang Y;Wang F;Yu J;Xu J;Yu J;Yi P

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RNA结合蛋白(RBP)是一组参与转录后调节以维持细胞稳态的蛋白质。卵巢癌(OC)是最致命的妇科癌症,但RBP在OC中的作用尚未完全了解。在此,我们报道了在浆液性OC患者中,RBP QKI 5与侵袭性肿瘤分期和预后不良呈显著负相关。QKI 5在体内外均能抑制OC细胞的生长和转移。转录组分析显示,QKI 5负调控转录共激活因子TAZ及其下游靶点(例如,CTGF和CYR61)。在机制上,QKI 5与TAZ mRNA结合并募集EDC 4,从而降低TAZ mRNA的稳定性。在功能上,TAZ参与了QKI 5介导的OC细胞的肿瘤抑制,并且在OC患者中QKI 5表达与TAZ、CTGF和CYR61表达呈负相关。总之,我们的研究表明QKI 5发挥肿瘤抑制作用并负调节OC中TAZ的表达。卵巢癌是最致命的妇科恶性肿瘤,本文报道了RNA结合蛋白QKI 5通过促进转录辅激活因子TAZ mRNA的降解并负性调节其表达,从而抑制卵巢癌细胞的生长和转移。
RNA-binding proteins (RBPs) are a set of proteins involved in many steps of post-transcriptional regulation to maintain cellular homeostasis. Ovarian cancer (OC) is the most deadly gynecological cancer, but the roles of RBPs in OC are not fully understood. Here, we reported that the RBP QKI5 was significantly negatively correlated with aggressive tumor stage and worse prognosis in serous OC patients. QKI5 could suppress the growth and metastasis of OC cells both in vitro and in vivo. Transcriptome analysis showed that QKI5 negatively regulated the expression of the transcriptional coactivator TAZ and its downstream targets (e.g., CTGF and CYR61). Mechanistically, QKI5 bound to TAZ mRNA and recruited EDC4, thus decreasing the stability of TAZ mRNA. Functionally, TAZ was involved in the QKI5-mediated tumor suppression of OC cells, and QKI5 expression was inversely correlated with TAZ, CTGF, and CYR61 expression in OC patients. Together, our study indicates that QKI5 plays a tumor-suppressive role and negatively regulates TAZ expression in OC. Ovarian cancer is the most deadly gynecological cancer, and here we reported that the RNA binding protein QKI5 could suppress the growth and metastasis of ovarian cancer cells through promoting the transcriptional coactivator TAZ mRNA decay and negatively regulating its expression.
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