LncRNA H19 Promotes Lung Adenocarcinoma Progression via Binding to Mutant p53 R175H

SIMPLE SUMMARY: This research explored the association and interaction between lncRNA H19 and mutant p53 (R175H) in lung adenocarcinoma development and progression. H19 over-expression may induce the elevated expression of mtp53 and interact with mtp53, which prolongs the p53 half-life and promotes transcriptional activity, leading to the progression of lung adenocarcinoma. The simultaneous inhibition of H19 and mtp53 may provide a novel strategy. ABSTRACT: Background: Accumulating data suggest that long non-coding RNA (lncRNA) H19 and p53are closely related to the prognosis of lung cancer. This study aims to analyze the association and interaction betweenH19 and mutant p53 R175H in lung adenocarcinoma (LAC). Methods: Mutant-type (Mt) p53 R175H was assessed by using RT-PCR in LAC cells and 100 cases of LAC tissue samples for association with H19 expression. Western blot, RNA-pull down, immunoprecipitation-Western blot and animal experiments were used to evaluate the interaction between H19 and mtp53. Results: Mtp53 R175H and H19 were over-expressed in LAC tissues and cells, while H19 over-expression extended the p53 half-life and enhanced transcriptional activity. Combined with anti-p53, ShH19 can significantly inhibit tumor growth in vivo. Conclusions: H19 over-expression may induce the elevated expression of mtp53 and interact with mtp53, leading to LAC progression. In addition, the high expression of mtp53 R175H is associated with poor overall survival inpatients. The simultaneous inhibition of H19 and mtp53 may provide a novel strategy for the effective control of LAC clinically.