MRPL35 Is Up-Regulated in Colorectal Cancer and Regulates Colorectal Cancer Cell Growth and Apoptosis.

Abstract

Mitochondrial ribosome proteins (MRPs), which are encoded by the nuclear genomic DNA, are important for mitochondrial-encoded protein synthesis and mitochondrial function. Emerging evidence suggests that several MRPs also exhibit important extra-mitochondrial functions, such as involvement in apoptosis, protein biosynthesis, and signal transduction. In this study, we demonstrate a significant role of MRP L35 (MRPL35) in colorectal cancer (CRC). The expression of MRPL35 was higher in CRC tissues than in matched cancer-adjacent tissues and higher in CRC cells than in normal mucosal epithelial cells. Higher MRPL35 expression in CRC tissue correlated with shorter overall survival for CRC patients. In vitro, down-regulation of MRPL35 led to increased production of reactive oxygen species (ROS) together with DNA damage, loss of cell proliferation, G2/M arrest, a decrease in mitochondrial membrane potential, apoptosis, and autophagy induction. MRPL35 knockdown inhibited tumor proliferation in a CRC xenograft nude mouse model. Furthermore, overexpression of MRPL35 or treatment of cells with the ROS scavenger, N-acetyl cysteine, abrogated ROS production, cell cycle arrest, and apoptosis in vitro. These findings suggest that MRPL35 plays an essential role in the development of CRC and may be a potential therapeutic target for CRC.

• Authors: Litao Zhang, Peifen Lu, Lihong Yan, Lijun Yang, Yutao Wang, Junjun Chen, Jie Dai, Yahui Li, Zhiming Kang, Tao Bai, Yanfeng Xi, Jun Xu, Gongqin Sun, Tao Yang
• Journal: The American journal of pathology (Am J Pathol) Vol. 189 Issue 5 Pg. 1105-1120 (05 2019) ISSN: 1525-2191 [Electronic] United States
• PMID: 30862482 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers, Tumor
• MRPL35 protein, human
• Mitochondrial Proteins
• Ribosomal Proteins

Topics

• Animals
• Apoptosis
• Biomarkers, Tumor (genetics, metabolism)
• Cell Cycle
• Cell Proliferation
• Colorectal Neoplasms (genetics, metabolism, pathology)
• Follow-Up Studies
• Gene Expression Regulation, Neoplastic
• Humans
• Male
• Mice
• Mice, Nude
• Mitochondrial Proteins (genetics, metabolism)
• Prognosis
• Ribosomal Proteins (genetics, metabolism)
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays