ABSTRACT
Colorectal cancer (CRC) is the third commonest cancer globally, with metastasis being the reason for cancer-associated mortality. Much is still unknown biochemically about CRC, and with current treatments that are not wholly effective over time, new therapeutics are urgently needed. Emerging evidence has shown the importance of non-coding RNAs such as lncRNAs and miRNAs functions in the development and progression of CRC. However, the exact underlying mechanism of these types of RNAs in CRC is still mostly unknown. PI3K/AKT/mTOR pathway contributes to many cellular processes, and dysregulation of this pathway frequently occurs in cancers. In this review, the authors have mostly focused on the significant non-coding RNAs regulators of the PI3K/AKT/mTOR pathway and their contribution to the development or inhibition of CRC and their potential as diagnostic or therapeutic targets in CRC treatment.
Subject(s)
Colorectal Neoplasms , MicroRNAs/metabolism , RNA, Long Noncoding/metabolism , Signal Transduction , TOR Serine-Threonine Kinases/metabolism , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Gene Expression Regulation, Neoplastic , Humans , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolismABSTRACT
Various post-translational lens crystallins modifications result in structural and functional insults, contributing to the development of lens opacity and cataract disorders. Lens crystallins are potential targets of homocysteinylation, particularly under hyperhomocysteinemia which has been indicated in various eye diseases. Since both homocysteinylation and acetylation primarily occur on protein free amino groups, we applied different spectroscopic methods and gel mobility shift analysis to examine the possible preventive role of acetylation against homocysteinylation. Lens crystallins were extensively acetylated in the presence of acetic anhydride and then subjected to homocysteinylation in the presence of homocysteine thiolactone (HCTL). Extensive acetylation of the lens crystallins results in partial structural alteration and enhancement of their stability, as well as improvement of α-crystallin chaperone-like activity. In addition, acetylation partially prevents HCTL-induced structural alteration and aggregation of lens crystallins. Also, acetylation protects against HCTL-induced loss of α-crystallin chaperone activity. Additionally, subsequent acetylation and homocysteinylation cause significant proteolytic degradation of crystallins. Therefore, further experimentation is required in order to judge effectively the preventative role of acetylation on the structural and functional insults induced by homocysteinylation of lens crystallins.