LINC00926 promotes progression of renal cell carcinoma via regulating miR-30a-5p/SOX4 axis and activating IFNγ-JAK2-STAT1 pathway.

Oct 23, 2023

Experts: Lin Du,Baojun Wang,Mengtong Wu,Weixu Chen,Wendi Wang,Wenli Diao,Meng Ding,Wei Chen,Wenmin Cao,Hongqian Guo,Gutian Zhang

The role of long non-coding RNA (lncRNA) in the progression of renal cell carcinoma (RCC) remains further study. Whether lncRNA may be used to predict the immunotherapy efficacy of RCC is less studied. In this study, LINC00926 was found to be mainly located in cytoplasm by FISH and RNA nuclear-cytoplasmic fractionation. Downregulation of LINC00926 in RCC cell lines inhibited the progression and metastasis of RCC cells. RNA pull-down assay and dual-luciferase reporter assay demonstrated that LINC00926 functioned as miR-30a-5p sponge to facilitate SOX4 expression. LINC00926 overexpression in BALB/c mice enhanced PD-L1 surface expression and resulted in immune escape. Mechanistic investigations showed that LINC00926 competitively bound to Lyn, leading to the inhibition of CBL-mediated ubiquitination and degradation, and stabilized Lyn, contributing to the activation of IFNγ-JAK2-STAT1 signaling pathway. Moreover, LINC00926, together with PD-L1 or PD-1 expression, may predict the overall survival in RCC patients. Therefore, LINC00926 has the potential to be a novel therapeutic target and a biomarker to predict ICB immunotherapy response in RCC.
Copyright © 2023. Published by Elsevier B.V.

Author

admin

View all posts

ABOUT THE EXPERTS

Lin Du,Baojun Wang,Mengtong Wu,Weixu Chen,Wendi Wang,Wenli Diao,Meng Ding,Wei Chen,Wenmin Cao,Hongqian Guo,Gutian Zhang

Lin Du

Department of Urology, Nanjing Drum Tower Hospital Clinical College of Southeast University, Nanjing, 210008, Jiangsu, China; Department of Urology, The First People’s Hospital of Yancheng, Yancheng, 224006, Jiangsu, China.

Baojun Wang

Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230039, Anhui, China; Department of Urology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, 210008, Jiangsu, China.

Mengtong Wu

Department of Urology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, 210008, Jiangsu, China.

Weixu Chen

Department of Urology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, 210008, Jiangsu, China.

Wendi Wang

Department of Urology, Nanjing Drum Tower Hospital Clinical College of Southeast University, Nanjing, 210008, Jiangsu, China.

Wenli Diao

Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University, Nanjing, 210008, Jiangsu, China.

Meng Ding

Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University, Nanjing, 210008, Jiangsu, China.

Wei Chen

Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University, Nanjing, 210008, Jiangsu, China.

Wenmin Cao

Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University, Nanjing, 210008, Jiangsu, China.

Hongqian Guo

Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University, Nanjing, 210008, Jiangsu, China. Electronic address: dr.ghq@nju.edu.cn.

Gutian Zhang

Department of Urology, Nanjing Drum Tower Hospital Clinical College of Southeast University, Nanjing, 210008, Jiangsu, China; Department of Urology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, 210008, Jiangsu, China. Electronic address: zhang.gutian@nju.edu.cn.