Identification of leucine-rich repeat-containing protein 59 (LRRC59) located in the endoplasmic reticulum as a novel prognostic factor for urothelial carcinoma.
Identification of leucine-rich repeat-containing protein 59 (LRRC59) located in the endoplasmic reticulum as a novel prognostic factor for urothelial carcinoma.
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DOI：
10.1016/j.tranon.2022.101474
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发表时间：
2022-09
影响因子：
5
通讯作者：
Lin, Qiongqiong
中科院分区：
文献类型：
--
作者：
Pei, Lu;Zhu, Qingfeng;Zhuang, Xiaoping;Ruan, Honglian;Zhao, Zhiguang;Qin, Haide;Lin, Qiongqiong
关键词：
LRRC 59是一种位于内质网（ER）的富含亮氨酸重复序列的蛋白质，是一种新的UC预测生物标志物。LRRC 59蛋白表达水平的升高与UC的病理分级和分期有关。LRRC 59的敲低可显着抑制细胞增殖和迁移，导致细胞周期停滞在G1期，而UC细胞中过表达LRRC 59可增强细胞增殖和迁移。LRRC 59的功能网络涉及蛋白质错误折叠、内质网应激和泛素化过程。体外实验证明LRRC 59调节ER应激信号传导。尿路上皮癌（UC）是全球最常见的癌症之一。UC的生物学异质性给预测治疗结果带来相当大的困难，通常导致临床管理不善。识别更灵敏、更有效的预测生物标志物对于UC的诊断和分类非常重要。在此，我们报告了位于内质网的富含亮氨酸重复序列的蛋白59（LRRC 59）作为一种新的预测因子和潜在的治疗靶点UC。在我们的107例UC样本队列中使用全载玻片图像分析，我们进行免疫组织化学以评估UC中LRRC 59表达的预后价值。利用RNAi技术进行体外实验，以探讨LRRC 59在促进UC细胞增殖和迁移中的作用。在我们的队列中，LRRC 59与UC的不良预后之间存在显著相关性。随后的临床分析也显示，LRRC 59的表达水平升高与UC的较高病理分级和晚期显著相关。随后，使用小干扰RNA敲低UM-UC-3和T24细胞中的LRRC 59显著抑制细胞增殖和迁移，导致细胞周期停滞在G1期。相反，LRRC 59在UC细胞中的过表达增强了细胞增殖和迁移。一个综合的生物信息学分析揭示了一个重要的功能网络LRRC 59涉及蛋白质错误折叠，ER应力，和泛素化。最后，体外实验证明LRRC 59调节ER应激信号传导。LRRC 59表达与UC预后显著相关。LRRC 59不仅可以作为UC患者风险分层的新的预后生物标志物，而且还可以作为UC的潜在治疗靶点，值得进一步研究。
LRRC59, a leucine-rich repeat-containing protein located at the endoplasmic reticulum (ER), is a novel predictive biomarker of UCs. The elevated expression levels of LRRC59 protein were significantly associated with UC higher pathological grades and advanced stages. Knockdown of LRRC59 significantly inhibited cell proliferation, migration and resulted in cell cycle arrest at G1 phase, while over-expressing LRRC59 in UC cells enhanced cell proliferation and migration. The functional network of LRRC59 involved protein misfolding, ER stress and ubiquitination process. In vitro experiments demonstrated that LRRC59 modulates ER stress signaling. Urothelial carcinoma (UC) is one of the most common cancers worldwide. The biological heterogeneity of UCs causes considerable difficulties in predicting treatment outcomes and usually leads to clinical mismanagement. The identification of more sensitive and efficient predictive biomarkers is important in the diagnosis and classification of UCs. Herein, we report leucine-rich repeat-containing protein 59 (LRRC59) located in the endoplasmic reticulum as a novel predictive factor and potential therapeutic target for UCs. Using whole-slide image analysis in our cohort of 107 UC samples, we performed immunohistochemistry to evaluate the prognostic value of LRRC59 expression in UCs. In vitro experiments using RNAi were conducted to explore the role of LRRC59 in promoting UC cell proliferation and migration. A significant correlation between LRRC59 and unfavorable prognosis of UCs in our cohort was demonstrated. Subsequent clinical analysis also revealed that elevated expression levels of LRRC59 were significantly associated with higher pathological grades and advanced stages of UC. Subsequently, knockdown of LRRC59 in UM-UC-3 and T24 cells using small interfering RNA significantly inhibited cell proliferation and migration, resulting in cell cycle arrest at the G1 phase. Conversely, the overexpression of LRRC59 in UC cells enhanced cell proliferation and migration. An integrated bioinformatics analysis revealed a significant functional network of LRRC59 involving protein misfolding, ER stress, and ubiquitination. Finally, in vitro experiments demonstrated that LRRC59 modulates ER stress signaling. LRRC59 expression was significantly correlated with UC prognosis. LRRC59 might not only serve as a novel prognostic biomarker for risk stratification of patients with UC but also exhibit as a potential therapeutic target in UC that warrants further investigation.
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影响因子：
4.6
作者：
Bankhead P;Loughrey MB;Fernández JA;Dombrowski Y;McArt DG;Dunne PD;McQuaid S;Gray RT;Murray LJ;Coleman HG;James JA;Salto-Tellez M;Hamilton PW
通讯作者：
Hamilton PW
影响因子：
28.2
作者：
Dominguez, Claudia X.;Mueller, Soren;Turley, Shannon J.
通讯作者：
Turley, Shannon J.
DOI：
10.1074/mcp.m115.050401
发表时间：
2016-01
期刊：
Molecular & cellular proteomics : MCP
影响因子：
--
作者：
Maurizio E;Wiśniewski JR;Ciani Y;Amato A;Arnoldo L;Penzo C;Pegoraro S;Giancotti V;Zambelli A;Piazza S;Manfioletti G;Sgarra R
通讯作者：
Sgarra R
影响因子：
5.6
作者：
Blenski, Marina;Kehlenbach, Ralph H.
通讯作者：
Kehlenbach, Ralph H.
影响因子：
4
作者：
Li, Dong;Xing, Ying;Qian, Jing
通讯作者：
Qian, Jing