
Asia Pacific Academy of Science Pte. Ltd. (APACSCI) specializes in international journal publishing. APACSCI adopts the open access publishing model and provides an important communication bridge for academic groups whose interest fields include engineering, technology, medicine, computer, mathematics, agriculture and forestry, and environment.

Proteomic Profiling of Recurrent Colorectal Cancer Reveals RICTOR with Cancer-Promoting Role by Downregulating Mitochondrial Oxidative Phosphorylation
Vol 38, Issue 3, 2024
Abstract
Background: Colorectal cancer (CRC), ranking as the second leading cause of global cancer-related deaths, is marked by a high recurrence rate. Metabolic reprogramming, a characteristic feature of CRC, involves a shift from mitochondrial oxidative phosphorylation (OXPHOS) to glycolysis to fuel cell proliferation. However, the regulatory mechanisms of OXPHOS in CRC recurrence remain unclear. Methods: Proteomic analysis was conducted using CRC tissues from recurrent and non-recurrent patients. Candidate proteins identified through bioinformatic analysis were validated using Real-time quantitative PCR and western blot. Functional investigations were carried out through knockdown and overexpression strategies. Results: Our study revealed a correlation between CRC recurrence and reduced OXPHOS levels. Meanwhile, an upregulation of rapamycin-insensitive companion of mTOR (RICTOR) was observed in recurrent patients, correlating with a poorer CRC prognosis. RICTOR inhibited the expression of subunits of OXPHOS complexes, including NADH-ubiquinone oxidoreductase core subunit V2 (NDUFV2), NADH dehydrogenase (ubiquinone) 1 beta subcomplex 8 (NDUFB8), succinate dehydrogenase complex, subunit B (SDHB), and cytochrome c oxidase 5A (COX5A). Overexpression of RICTOR suppressed mitochondrial OXPHOS and promoted cell proliferation. Conversely, RICTOR knockdown reversed enhanced cell proliferation and inhibited subcutaneous tumor growth. Conclusion: In summary, our findings suggest that elevated RICTOR expression disrupts the assembly of the mitochondrial electron respiratory chain, consequently suppressing OXPHOS levels and ultimately promoting CRC recurrence.
Keywords
References
Supporting Agencies
Copyright (c) 2024 Zhenyu Jia, Yongda Lu, Lu Zheng, Jiaqing Shen, Chenyue Tang, Yuqi Shi, Lijuan Qian, Tingting Xia
This site is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Medical Genetics, University of Torino Medical School, Italy

Department of Biomedical, Surgical and Dental Sciences, University of Milan, Italy