LRPPRC regulates redox homeostasis via the circANKHD1/FOXM1 axis to enhance bladder urothelial carcinoma tumorigenesis.
LRPPRC regulates redox homeostasis via the circANKHD1/FOXM1 axis to enhance bladder urothelial carcinoma tumorigenesis.
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LRPPRC 通过 circANKHD1/FOXM1 轴调节氧化还原稳态，增强膀胱尿路上皮癌肿瘤发生
DOI：
10.1016/j.redox.2021.102201
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发表时间：
2021-11-27
期刊：
影响因子：
11.4
通讯作者：
Yu CP
中科院分区：
文献类型：
--
作者：
Wei WS;Wang N;Deng MH;Dong P;Liu JY;Xiang Z;Li XD;Li ZY;Liu ZH;Peng YL;Li Z;Jiang LJ;Yao K;Ye YL;Lu WH;Zhang ZL;Zhou FJ;Liu ZW;Xie D;Yu CP
活性氧（Reactive oxygen species，ROS）主要由线粒体持续产生，在肿瘤细胞的应激信号转导中起重要作用。此外，五肽重复序列（PPR）蛋白已被建议参与线粒体代谢。然而，整合这些不同的网络在膀胱尿路上皮癌（UCB）发病机制的作用是难以捉摸的。在这项研究中，我们发现富含亮氨酸的五肽重复序列（LRPPRC）在UCB中频繁上调，并且它是UCB的独立预后因素。我们进一步揭示了LRPPRC通过调节细胞内ROS稳态促进UCB肿瘤发生。从机制上讲，LRPPRC通过mt-mRNA代谢和circANKHD 1/FOXM 1轴调节ROS平衡并保护UCB细胞免受氧化应激。此外，SRA茎环相互作用RNA结合蛋白（SLIRP）直接与LRPPRC相互作用，以保护其免受泛素化和蛋白酶体降解。值得注意的是，我们发现LRPPRC以circANKHD 1-FOXM 1依赖的方式调节UCB细胞的肿瘤发生。总之，LRPPRC在调节UCB氧化还原稳态和肿瘤发生中发挥关键作用，并且是UCB的预后因素;这表明LRPPRC可以作为UCB中可利用的治疗靶点。LRPPRC在UCB中过表达，是独立的预后生物标志物。LRPPRC通过调节细胞内ROS稳态促进UCB肿瘤发生。LRPPRC通过mt-mRNA和circANKHD 1/FOXM 1保护UCB细胞免受氧化应激。LRPPRC以circANKHD 1-FOXM 1依赖的方式促进UCB的肿瘤发生。
Reactive oxygen species (ROS) which are continuously generated mainly by mitochondria, have been proved to play an important role in the stress signaling of cancer cells. Moreover, pentatricopeptide repeat (PPR) proteins have been suggested to take part in mitochondrial metabolism. However, the mechanisms integrating the actions of these distinct networks in urothelial carcinoma of the bladder (UCB) pathogenesis are elusive. In this study, we found that leucine rich pentatricopeptide repeat containing (LRPPRC) was frequently upregulated in UCB and that it was an independent prognostic factor in UCB. We further revealed that LRPPRC promoted UCB tumorigenesis by regulating the intracellular ROS homeostasis. Mechanistically, LRPPRC modulates ROS balance and protects UCB cells from oxidative stress via mt-mRNA metabolism and the circANKHD1/FOXM1 axis. In addition, the SRA stem-loop interacting RNA binding protein (SLIRP) directly interacted with LRPPRC to protect it from ubiquitination and proteasomal degradation. Notably, we showed that LRPPRC modulated the tumorigenesis of UCB cells in a circANKHD1-FOXM1-dependent manner. In conclusion, LRPPRC exerts critical roles in regulating UCB redox homeostasis and tumorigenesis, and is a prognostic factor for UCB; suggesting that LRPPRC may serve as an exploitable therapeutic target in UCB. LRPPRC is overexpressed in UCBs and is an independent prognostic biomarker. LRPPRC promotes UCB tumorigenesis by regulating the intracellular ROS homeostasis. LRPPRC protects UCB cells from oxidative stress via mt-mRNA and circANKHD1/FOXM1. LRPPRC promotes the tumorigenesis of UCB in a circANKHD1-FOXM1-dependent manner.
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影响因子：
13.6
作者：
Kühl I;Miranda M;Posse V;Milenkovic D;Mourier A;Siira SJ;Bonekamp NA;Neumann U;Filipovska A;Polosa PL;Gustafsson CM;Larsson NG
通讯作者：
Larsson NG
DOI：
10.1126/science.1211485
发表时间：
2011-12-02
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Anastasiou D;Poulogiannis G;Asara JM;Boxer MB;Jiang JK;Shen M;Bellinger G;Sasaki AT;Locasale JW;Auld DS;Thomas CJ;Vander Heiden MG;Cantley LC
通讯作者：
Cantley LC
影响因子：
4.1
作者：
Lightowlers RN;Chrzanowska-Lightowlers ZM
通讯作者：
Chrzanowska-Lightowlers ZM
影响因子：
11.4
作者：
Choi, Hae-Ji;Jhe, Yoo-Lim;Cheong, Jae-Ho
通讯作者：
Cheong, Jae-Ho
影响因子：
3.5
作者：
Davies, Stefan M. K.;Rackham, Oliver;Filipovska, Aleksandra
通讯作者：
Filipovska, Aleksandra