Fig. 7: Effect of Comp34 on tumor growth in vivo. | Cell Death & Disease

Fig. 7: Effect of Comp34 on tumor growth in vivo.

From: Comp34 displays potent preclinical antitumor efficacy in triple-negative breast cancer via inhibition of NUDT3-AS4, a novel oncogenic long noncoding RNA

Fig. 7

a Tumor volume of MDA-MB-231 cells transplanted into female athymic nude mice (nu/nu) and treated with vehicle (n = 10), rapamycin (5 mg/kg, i.p., n = 12), or Comp34 (5 mg/kg, i.p., n = 12) once every 2 days for 4 weeks. b body weight was checked every 3 days. *P < 0.05 versus control; #P < 0.05 versus rapamycin. c Paraffin sections of xenograft tumor tissues were subjected to immunohistochemical (IHC) staining using the antibodies indicated. d Staining score of IHC analysis of AKT1 and mTOR. p value was calculated by one-way ANOVA. ***p < 0.001 vs control. e The identified signaling pathway in this study indicated that Comp34 represses TNBC growth via inhibition of AKT1/mTOR mRNA and protein expression. Long noncoding RNA (lncRNA) -NUDT3-AS4 acts as a microRNA sponge to compete with AKT1/mTOR mRNAs for binding to miR-99s, leading to decrease in degradation of AKT1/mTOR mRNAs and subsequent increase in AKT1/mTOR protein expression, which promotes TNBC growth and progression. Comp34-induced miR-99s dissociation from NUDT3-AS4 and resultant degradation of NUDT3-AS4 through the NMD pathway lead to increase in miR-99s-dependent degradation of AKT1/mTOR mRNA in TNBCs, subsequently inhibiting AKT1/mTOR protein expression and TNBC development.

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