Fig. 3: LncRNAs regulate the autophagy pathways in NSCLC.
From: Targeting lncRNAs in programmed cell death as a therapeutic strategy for non-small cell lung cancer
Autophagy starts with the formation of phagophores. The formation of unc-51-like kinase (ULK) complex from ULK1/2 kinase, ATG13, ATG101 and family-interacting protein FIP200, directly modulated by integrated signals from the mechanistic target of rapamycin complex 1 (mTORC1) and AMP-activated protein kinase (AMPK) signalling, triggers autophagic activity. Activated ULK1 can lead to the phosphorylation of Beclin1, thus activating class III PI3-kinase (VPS34) complex, which consists of VPS34, Beclin-1, VPS15 and ATG14L, primarily responsible for the nucleation of autophagosomal membrane. Two principal ubiquitination systems, ATG5-ATG12 and LC3 conjugation systems participate in autophagophore elongation and conversion into intact autophagosome. Respectively, ATG5 and ATG12 assemble into a complex, which then interacts with ATG16L1 to form a multimeric ATG12-ATG5-ATG16L1 conjugate that is on the outer surface of the autophagosomal membrane. Membrane-bound LC3-II is generated by the conjugation of microtubule-associated protein 1-light chain 3-I (LC3-I) to the lipid phosphatidylethanolamine (PE), providing a docking site for mounting autophagy cargo receptors that enable cargo loading into the autophagic vesicles. Various oncogenic lncRNAs (red font, high expression in NSCLC) participate in lung cancer-associated autophagy by regulating autophagy-related proteins.
