ABSTRACT
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 axis. Based on early research from our laboratory, we selected LINC00176 for further exploration. LINC00176 levels were affected by the overexpression and knockdown of Δ40p53. Further, under DNA damage, ER stress, and glucose deprivation, LINC00176 was upregulated in HCT116 p53-/- cells (harboring only Δ40p53) compared to HCT116 p53+/+ cells. Additionally, ChIP and RNA stability assays revealed that Δ40p53 transactivates LINC00176 transcriptionally and stabilizes it post-transcriptionally. We ectopically overexpressed and knocked down LINC00176 in HCT116 p53-/- cells, which affected proliferation, cell viability, and the expression of epithelial markers. Finally, RNA pulldown revealed that LINC00176 sequesters several putative miRNA targets. These results provide important insights into the pivotal role of Δ40p53 in regulating the lncRNA-miRNA axis.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
While entering the author information, the order was reversed by mistake, which we have corrected now in this version as per the uploaded MS text.