Epigenetic regulation of autophagy by non-coding RNAs in gastrointestinal tumors: Biological functions and therapeutic perspectives

Abstract

Cancer is the manifestation of changes and mutations in genetic and epigenetic levels. Non-coding RNAs (ncRNAs) are commonly dysregulated in disease pathogenesis, and their role in cancer has been well-documented. The ncRNAs regulate various molecular pathways and mechanisms in cancer that can lead to induction/inhibition of carcinogenesis. Autophagy is a molecular “self-digestion” mechanism its function can be pro-survival or pro-death in tumor cells. The aim of the present review is to evaluate the role of ncRNAs in regulating autophagy in gastrointestinal tumors. The role of the ncRNA/autophagy axis in affecting the progression of gastric, liver, colorectal, pancreatic, esophageal, and gallbladder cancers is investigated. Both ncRNAs and autophagy mechanisms can function as oncogenic or onco-suppressor and this interaction can determine the growth, invasion, and therapy response of gastrointestinal tumors. ncRNA/autophagy axis can reduce/increase the proliferation of gastrointestinal tumors via the glycolysis mechanism. Furthermore, related molecular pathways of metastasis, such as EMT and MMPs, are affected by the ncRNA/autophagy axis. The response of gastrointestinal tumors to chemotherapy and radiotherapy can be suppressed by pro-survival autophagy, and ncRNAs are essential regulators of this mechanism. miRNAs can regulate related genes and proteins of autophagy, such as ATGs and Beclin-1. Furthermore, lncRNAs and circRNAs down-regulate miRNA expression via sponging to modulate the autophagy mechanism. Moreover, anti-cancer agents can affect the expression level of ncRNAs regulating autophagy in gastrointestinal tumors. Therefore, translating these findings into clinics can improve the prognosis of patients.