lncRNAs regulate downstream gene functions, including the well-established regulation of the competing endogenous RNA (ceRNA) pathway. Our study revealed that overexpressed LINC00665 significantly decreased the mRNA expression levels of MTF1 and YY2, while STAU1 knockdown rescued their depletion induced by LINC00665 overexpression. Further investigation of the underlying mechanism demonstrated that LINC00665 might facilitate the degradation of MTF1 and YY2 mRNA by interacting with STAU1. The SMD pathway is a translation-dependent mechanism that ubiquitously exists in mammalian cells.44 Alu elements on lncRNAs were suggested to directly bind to Alu elements on the 3′ UTR of the target mRNA in the complementary base-pairing pattern via a STAU1-binding site.45 When translation is terminated sufficiently upstream of the SBS, STAU1 bound to the SBS might recruit and bind to UPF1, inducing the mRNA degradation process and therefore shortening the half-life of the target mRNA and activating the SMD pathway.46, 47, 48 Using the bioinformatics software RepeatMasker and IntaRNA, we predicted the putative SBS between the Alu element on LINC00665 and the Alu element on either the MTF1 or YY2 mRNA 3′ UTR, which was
