The Emerging Role of Stress Granules in Hepatocellular Carcinoma

Abstract

Stress granules (SGs) are small membrane-free cytosolic liquid-phase ordered entities in which mRNAs are protected and translationally silenced during cellular adaptation to harmful conditions (e.g., hypoxia, oxidative stress). This function is achieved by structural and functional SG components such as scaffold proteins and RNA-binding proteins controlling the fate of mRNAs. Increasing evidence indicates that the capacity of cells to assemble/disassemble functional SGs may significantly impact the onset and the development of metabolic and inflammatory diseases, as well as cancers. In the liver, the abnormal expression of SG components and formation of SG occur with chronic liver diseases, hepatocellular carcinoma (HCC), and selective hepatic resistance to anti-cancer drugs. Although, the role of SG in these diseases is still debated, the modulation of SG assembly/disassembly or targeting the expression/activity of specific SG components may represent appealing strategies to treat hepatic disorders and potentially cancer. In this review, we discuss our current knowledge about pathophysiological functions of SGs in HCC as well as available molecular tools and drugs capable of modulating SG formation and functions for therapeutic purposes.

WITHDRAWN: Paired stress granule gene signatures predict survival and inform immune status in hepatocellular carcinoma

“…The purpose of our study was to identify critical and novel biomarkers associated with the progression and development of HCC, with increasing evidence pointing towards the signi cant role of SGs in HCC progression. Deregulated expressions of these SG regulator by various mechanisms are frequently observed in HCC (10). Although the prognostic signi cance of SG regulators in HCC has not been studied, this research established a novel prognostic risk scoring model using a paired SG gene signature approach, which has the potential to be a valuable clinical tool for predicting clinical outcomes in HCC patients.…”

“…Moreover, studies has revealed SGs exhibit various prognostic markers in prostate cancer (7), pancreatic cancer (8), and nasopharyngeal carcinoma (9). Furthermore, growing evidence suggests that SGs play a key role in promoting HCC progression (10). Although many genes related to SGs have been explored in HCC development, their prognostic signi cance still needs further analysis.…”

Ferroptosis in Hepatocellular Carcinoma: Mechanisms, Drug Targets and Approaches to Clinical Translation

“…A central component of SGs, the Ras-GTPase-activating protein SH3 domain-binding protein 1 (G3BP1), can be bound by the long noncoding RNA P53RRA which, in turn, leads to the higher retention of p53 in the cell nucleus accompanied by increased ferroptosis [ 99 ]. Another association between ferroptosis and SGs is based on the ELAVL1/HuR protein ((embryonic lethal, abnormal vision, Drosophila)-like 1, Hu-antigen R) which accumulates in SGs during cellular stresses and might confer a cell survival advantage via the stabilization of several oncogenic transcripts (for details, see e.g., [ 100 ]). Interestingly, while HuR expression correlates with a poor clinical outcome in HCC [ 101 ], it additionally promotes ferroptosis induced by sorafenib [ 102 ]; however, a causal link between sorafenib resistance and SG formation remains to be investigated [ 100 ].…”

STRESS granule-associated RNA-binding protein CAPRIN1 drives cancer progression and regulates treatment response in nasopharyngeal carcinoma

“…The formation of SGs regulates cellular stress response in pathological conditions [ 13 ], including tumor progression and treatment response [ 15 ]. It has also been reported that stress particles play roles in hepatocellular carcinoma (HCC) [ 16 ] and colorectal cancer [ 17 ] et al However, the role and mechanism of stress granule formation within the context of oxidative stress and the effects on radiotherapy and chemotherapy for NPC are still unclear.…”