Protein misfolding and unfolded protein response in cancer: Current updates with focus on epigenetic regulation

The structure of proteins holds the key to their optimum functioning. Misfolding of proteins often renders them useless and the resulting aggregates are implicated in endoplasmic reticulum stress and the onset of several human diseases. Therefore, a robust system, spearheaded by unfolded protein response (UPR) is in place as a quality check. The unfolded proteins are cleared and marked for degradation. UPR pathway consists of multiple factors, such as the chaperone GRP78, and is often deregulated in cancers, thus presenting as an attractive target for therapy. Emerging evidence indicates epigenetic regulation of UPR with the involvement of non-coding RNAs, such as, microRNAs and long non-coding RNAs, as well as DNA methylation and histone modifications. Here, we provide an overview of UPR in tumorigenesis with a focus on mutual inter-regulatory relationship between UPR and non-coding RNAs. We also discuss the novel findings on transport of misfolded proteins in exosomes and the promising role of epigenetic drugs in modulation of UPR.