MIOX inhibits autophagy to regulate the ROS -driven inhibition of STAT3/c-Myc-mediated epithelial-mesenchymal transition in clear cell renal cell carcinoma
Longxiyu Meng,
Jie Gao,
Wenjing Mo,
Baojun Wang,
Hongwei Shen,
Wenmin Cao,
Meng Ding,
Wenli Diao,
Wei Chen,
Qing Zhang,
Jiaxin Shu,
Huiqi Dai,
Hongqian Guo
Affiliations
Longxiyu Meng
Department of Urology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Institute of Urology Nanjing University, Nanjing, Jiangsu, 210008, China
Jie Gao
Department of Urology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Institute of Urology Nanjing University, Nanjing, Jiangsu, 210008, China
Wenjing Mo
Department of Urology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210008, China
Baojun Wang
Department of Urology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210008, China
Hongwei Shen
Department of Urology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210008, China
Wenmin Cao
Department of Urology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Institute of Urology Nanjing University, Nanjing, Jiangsu, 210008, China
Meng Ding
Department of Urology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Institute of Urology Nanjing University, Nanjing, Jiangsu, 210008, China
Wenli Diao
Department of Urology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Institute of Urology Nanjing University, Nanjing, Jiangsu, 210008, China
Wei Chen
Department of Urology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Institute of Urology Nanjing University, Nanjing, Jiangsu, 210008, China
Qing Zhang
Department of Urology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Institute of Urology Nanjing University, Nanjing, Jiangsu, 210008, China
Jiaxin Shu
Department of Urology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210008, China
Huiqi Dai
Department of Urology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210008, China
Hongqian Guo
Department of Urology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Institute of Urology Nanjing University, Nanjing, Jiangsu, 210008, China; Corresponding author. No. 321 Zhongshan Road, Nanjing, Jiangsu Province, 210008, China.
The specific mechanism of clear cell renal cell carcinoma (ccRCC) progression, a pathological type that accounts for the highest proportion of RCC, remains unclear. In this study, bioinformatics analysis of scRNA-seq dataset in ccRCC revealed that MIOX was a gene specifically down-regulated in tumor epithelial cells of ccRCC. Analysis of the TCGA database further validated the association between decreased MIOX mRNA levels and ccRCC malignant phenotype and poor prognosis. Immunohistochemistry indicated the down-regulation of MIOX in ccRCC tissues compared to paired adjacent renal tissues, with further down-regulation of MIOX in the primary tumors of patients with primary metastasis compared to those without metastasis. Also, patients with low expression of MIOX showed shorter metastasis-free survival (MFS) compared to those with high MIOX expression. In vitro results showed that overexpression of MIOX in ccRCC cells inhibited the proliferation, migration and invasion and promoted apoptosis. Mechanistically, up-regulation of MIOX inhibited autophagy to elevate the levels of ROS, and thus suppressed STAT3/c-Myc-mediated epithelial-mesenchymal transition in ccRCC cells. In vivo data further confirmed that increased MIOX expression suppressed the growth and proliferation of RCC cells and reduced the ability of RCC cells to form metastases in the lung. This study demonstrates that MIOX is an important regulatory molecule of ccRCC, which is conducive to understanding the potential molecular mechanism of ccRCC progression.
