Long non-coding RNAs: controversial roles in drug resistance of solid tumors mediated by autophagy.

ABSTRACT

Current genome-wide studies have indicated that a great number of long non-coding RNAs (lncRNAs) are transcribed from the human genome and appeared as crucial regulators in a variety of cellular processes. Many studies have displayed a significant function of lncRNAs in the regulation of autophagy. Autophagy is a macromolecular procedure in cells in which intracellular substrates and damaged organelles are broken down and recycled to relieve cell stress resulting from nutritional deprivation, irradiation, hypoxia, and cytotoxic agents. Autophagy can be a double-edged sword and play either a protective or a damaging role in cells depending on its activation status and other cellular situations, and its dysregulation is related to tumorigenesis in various solid tumors. Autophagy induced by various therapies has been shown as a unique mechanism of resistance to anti-cancer drugs. Growing evidence is showing the important role of lncRNAs in modulating drug resistance via the regulation of autophagy in a variety of cancers. The role of lncRNAs in drug resistance of cancers is controversial; they may promote or suppress drug resistance via either activation or inhibition of autophagy. Mechanisms by which lncRNAs regulate autophagy to affect drug resistance are different, mainly mediated by the negative regulation of micro RNAs. In this review, we summarize recent studies that investigated the role of lncRNAs/autophagy axis in drug resistance of different types of solid tumors.