The “LINC” in between Δ40p53-miRNA axis in the regulation of cellular homeostasis

Recently, we showed that Δ40p53, the translational isoform of p53, can inhibit cell growth independently of p53 by regulating microRNAs. Here, we explored the role of Δ40p53 in regulating the lncRNA-miRNA-cellular process axis and specifically focused on LINC00176 for further exploration. Interestingly, LINC00176 levels were affected predominantly by the overexpression/stress-mediated induction and knockdown of Δ40p53 compared to p53 levels. Additional assays revealed that Δ40p53 alone (and not p53) transactivates LINC00176 transcriptionally; however, both the proteins can directly bind to its RNA. Pulling down the RNA revealed that LINC00176 sequesters several putative miRNA targets, which could further titrate several mRNA targets involved in different cellular processes. Therefore, to understand the downstream effect of the regulation, we ectopically overexpressed and knocked down LINC00176 in HCT116 p53-/-(harboring only Δ40p53) cells which affected proliferation, cell viability, and the expression of epithelial markers. Our results provide essential insights into the pivotal role of Δ40p53 in regulating the novel LINC00176 RNA-miRNA-mRNA axis independent of FL-p53 and maintaining cellular homeostasis.