Ribosomal protein L10 in mitochondria serves as a regulator for ROS level in pancreatic cancer cells

Abstract

Tumorigenesis is commonly known as a complicated process, in which reactive oxygen species (ROS) plays a critical role to involve in signal transduction, metabolism, cell proliferation and differentiation. Previously, ribosomal protein L10 (RPL10) was suggested to possess extra-ribosomal functions in pancreatic cancer cells in addition to being proposed as a tumor suppressor or transcription co-regulator. To better understand the relationship between RPL10 and tumorigenic potential in pancreatic cancer cells, chromatin immunoprecipitation sequencing reveals that RPL10 is unlikely to be a transcription factor without a specific binding motif for gene transcription. Additionally, transcriptome analysis indicates that RPL10 could regulate the expression of proteins related to ROS production. Moreover, RPL10 in mitochondria is closely associated with the regulation of ROS level by affecting Complex I activity and the subsequent events. Together, the present study suggests that the regulation of ROS level by mitochondrial RPL10 is one of the major extra-ribosomal functions in pancreatic cancer cells, which could be used as an indicator for the tumorigenesis of pancreatic cancer.

Pathological Roles of Mitochondrial Oxidative Stress and Mitochondrial Dynamics in Cardiac Microvascular Ischemia/Reperfusion Injury

“…Their cellular toxicity comes from lipid peroxidation and its associated membrane damage [79,80]. DNA damage, oxidative post-transcriptional modification of cysteine residues in protein, and signal transduction are also governed by mtROS [81,82]. Due to the instability of free radical species, free radical scavengers have been utilized to directly prove the detrimental effects of mtROS in cardiac microvascular I/R injury.…”

Cancer Biogenesis in Ribosomopathies

“…By what mechanisms mutant ribosomes drive peroxisomal oxidation is unclear. Wild-type RPL10 (uL16) has also been described to regulate the expression of proteins related to ROS production and to control mitochondrial ROS production in pancreatic cancer [63]. It is therefore possible that RPL10-R98S (uL16-R98S) is no longer able to properly perform these ROS regulatory functions, but this requires further research.…”

Ribosomal protein QM/RPL10 positively regulates defence and protein translation mechanisms during nonhost disease resistance

“…QM10 was initially reported as a Wilm's tumour suppressor gene in humans and has homology with RPL10 (Rivera‐Madrid et al ., 1993; Shi et al ., 2004; Dong et al ., 2007; Chen et al ., 2011). QM/RPL10 interacts with c‐Jun transcription factor in humans and has been shown to be involved in regulating reactive oxygen species (ROS) levels in prostate cancer patients (Yang et al ., 2018). RPL10 is a 60S large subunit protein mainly involved in ribosome biogenesis and assembly of both large and small subunits (Eisinger et al ., 1997; Loftus et al ., 1997).…”