The Challenging Riddle about the Janus-Type Role of Hsp60 and Related Extracellular Vesicles and miRNAs in Carcinogenesis and the Promises of Its Solution

Abstract

Hsp60 is one of the most ancient and evolutionarily conserved members of the chaperoning system. It typically resides within mitochondria, in which it contributes to maintaining the organelle’s proteome integrity and homeostasis. In the last few years, it has been shown that Hsp60 also occurs in other locations, intracellularly and extracellularly, including cytosol, plasma-cell membrane, and extracellular vesicles (EVs). Consequently, non-canonical functions and interacting partners of Hsp60 have been identified and it has been realized that it is a hub molecule in diverse networks and pathways and that it is implicated, directly or indirectly, in the development of various pathological conditions, the Hsp60 chaperonopathies. In this review, we will focus on the multi-faceted role of this chaperonin in human cancers, showing the contribution of intra- and extracellular Hsp60 in cancer development and progression, as well as the impact of miRNA-mediated regulation of Hsp60 in carcinogenesis. There are still various aspects of this intricate biological scenario that are poorly understood but ongoing research is steadily providing new insights and we will direct attention to them. For instance, we will highlight the possible applications of the Hsp60 involvement in carcinogenesis not only in diagnosis, but also in the development of specific anti-cancer therapies centered on the use of the chaperonin as therapeutic target or agent and depending on its role, pro- or anti-tumor.

Molecular Pathways Implicated in Radioresistance of Glioblastoma Multiforme: What Is the Role of Extracellular Vesicles?

“…Other EV components, such as mRNA and miRNA, also have the potential as tumor diagnostic markers. miRNAs can be exchanged between cells via exosomes and their detection and analysis provides information about the parental cell [143,223,[235][236][237]. The diversity of transcriptomic profiles observed in glioma cells is mirrored in EVs derived from these cells.…”

Plant responses to temperature stress modulated by microRNAs

“…In contrast, wild‐type (WT) plants displayed higher heat stress tolerance (Wang et al 2017). Moreover, a pivotal aspect of the plant's reaction to heat stress involves the induction of a critical mitochondrial protein known as heat shock proteins ‐60 and 10 ( HSP60 and HSP10 ), triggered by the activation of heat stress transcription factors ( HSFs ) (David et al 2021). The rate of heat change dramatically alters the transcription level of HSF s and HSP s (Samakovli et al, 2020).…”

Interplay between the Chaperone System and Gut Microbiota Dysbiosis in Systemic Lupus Erythematosus Pathogenesis: Is Molecular Mimicry the Missing Link between Those Two Factors?

“…In the last few years, increasing evidence has pointed out the “other side of the coin” of the CS. In fact, when abnormal in structure/function/location/concentration, its members may become etiopathogenetic factors, causing diseases known as the chaperonopathies [ 10 , 11 , 12 ].…”

“…The involvement of Hsps in autoimmunity has been investigated for many years, and autoimmune diseases (ADs) can be classified into the group of chaperonopathies by mistake or collaborationism, i.e., acquired chaperonopathies in which a chaperone functions to favor the pathogenic mechanism and leads to disease [ 5 , 10 , 11 , 12 , 13 , 14 , 15 ]. However, their role is still under investigation.…”