PUF60/AURKA Axis Contributes to Tumor Progression and Malignant Phenotypes in Bladder Cancer.
PUF60/AURKA Axis Contributes to Tumor Progression and Malignant Phenotypes in Bladder Cancer.
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PUF60/AURKA 轴有助于膀胱癌的肿瘤进展和恶性表型。
DOI：
10.3389/fonc.2020.568015
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发表时间：
2020
影响因子：
4.7
通讯作者：
He L
中科院分区：
文献类型：
--
作者：
Long Q;An X;Chen M;Wang N;Sui S;Li Y;Zhang C;Lee K;Wang X;Tian T;Pan Y;Qiu H;Xie F;Deng W;Zheng F;He L
RNA剪接蛋白的异常表达或突变在人类癌症中被广泛观察到。在此，我们通过对TCGA膀胱癌表达数据的生物信息学分析，在97个RNA剪接蛋白中确定了聚(U)结合剪接因子60(PUF60)是正常组织和膀胱癌组织中差异表达最多的基因之一。PUF60在肿瘤组织中的表达显著升高，且PUF60的高表达与膀胱癌的恶性表型和生存期短有关。此外，我们还发现极光激酶A(AURKA)是PUF60在膀胱癌细胞中的一个新的下游靶点。PUF60基因敲除可显著抑制膀胱癌细胞的存活率和集落形成能力，而AURKA过表达则逆转了这一抑制作用。PUF60的过表达显著促进了膀胱癌细胞的存活和集落形成，而AURKA特异性抑制剂处理则逆转了这一促进作用。机制上，PUF60与AURKA启动子特异性结合，从而激活其转录和表达。此外，我们还发现PUF60和AURKA在膀胱癌组织中的表达呈显著正相关，并且PUF60和AURKA的表达与膀胱癌患者的肿瘤进展和恶性表型有关。综上所述，这些结果表明PUF60/AURKA轴在调节膀胱癌的发生和发展中起关键作用，可能成为膀胱癌患者潜在的预后生物标志物和治疗靶点。
Abnormal expression or mutation of RNA splicing proteins are widely observed in human cancers. Here, we identified poly(U) binding splicing factor 60 (PUF60) as one of the most differentially expressed genes out of 97 RNA splicing proteins between normal and bladder cancer tissues by bioinformatics analysis of TCGA bladder cancer expression data. The expression of PUF60 was significantly higher in tumor tissues, while high PUF60 expression was associated with malignant phenotypes of bladder cancer and shorter survival time. Moreover, we identified aurora kinase A (AURKA) as a new downstream target of PUF60 in bladder cancer cells. PUF60 knockdown significantly inhibited cell viability and colony formation capacity in bladder cancer cells, whereas AURKA overexpression reversed this inhibition effect. Overexpression of PUF60 significantly promoted cell viability and colony formation in bladder cancer cells, while treatment with AURKA specific inhibitor reversed this promotive effect. Mechanistically, PUF60 specifically bound to the AURKA promoter, thereby activating its transcription and expression. Furthermore, we showed that there was a significant positive correlation between PUF60 and AURKA expression in bladder cancer tissues, and PUF60 and AURKA expression contributed to tumor progression and malignant phenotypes in the patients with bladder cancer. Collectively, these results indicate that the PUF60/AURKA axis plays a key role in regulating tumorigenesis and progression of bladder cancer, and may be a potential prognostic biomarker and therapeutic target for bladder cancer patients.
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影响因子：
--
作者：
Kobayashi S;Hoshino T;Hiwasa T;Satoh M;Rahmutulla B;Tsuchida S;Komukai Y;Tanaka T;Matsubara H;Shimada H;Nomura F;Matsushita K
通讯作者：
Matsushita K
影响因子：
14.9
作者：
Královicová J;Ševcíková I;Stejskalová E;Obuca M;Hiller M;Stanek D;Vorechovský I
通讯作者：
Vorechovský I
影响因子：
--
作者：
Kim WT;Kim YH;Jeong P;Seo SP;Kang HW;Kim YJ;Yun SJ;Lee SC;Moon SK;Choi YH;Lee GT;Kim IY;Kim WJ
通讯作者：
Kim WJ
影响因子：
7.3
作者：
Busch, Anke;Hertel, Klemens J.
通讯作者：
Hertel, Klemens J.
DOI：
10.1042/bj20121248
发表时间：
2013-02-15
期刊：
The Biochemical journal
影响因子：
--
作者：
Coothankandaswamy V;Elangovan S;Singh N;Prasad PD;Thangaraju M;Ganapathy V
通讯作者：
Ganapathy V