Long Non-Coding RNA H19 Expression Correlates with Autophagy Process in Adrenocortical Carcinoma.
Pietro Di FazioFranziska D RuscheSilvia RothAnika PehlSabine WächterIoannis MintzirasDetlef K BartschKatharina HolzerPublished in: Cancer investigation (2021)
Adrenocortical carcinoma (ACC) is characterized by poor prognosis and high mortality. The suppression of the long-non-coding RNA H19, counterbalanced by IGF2 over-expression, leads to down-regulation of the autophagy markers, high proliferation rate and metastatic potential in patients affected by ACC. The administration of the deacetylase inhibitors (DACi) panobinostat, trichostatin A (TSA) and SAHA affected the cell viability of H295R monolayer and spheroids and induced the over-expression of H19 and autophagy transcripts. H19 knock down in H295R cells was not able to modulate the expression level of autophagy transcripts. Instead, H19 knock down was able to impede the ability of DACi to modulate the protein level of the autophagy markers. Furthermore, the administration of higher concentration of DACi was able to down-regulate the protein level of Beclin1 and p62 and to induce the conversion of LC3B-I into the active LC3B-II form, thus confirming an active autophagic process. Neither the active protein level nor the activity of caspases 8 and 3 was prompted by the DACi, thus excluding the involvement of the executioners of apoptosis in H295R decay. The DACi restore H19, the autophagy markers and trigger cell death in ACC cells. The re-activation of autophagy would represent a novel strategy for the treatment of patients affected by this severe malignancy.
Keyphrases
- poor prognosis
- cell death
- long non coding rna
- cell cycle arrest
- endoplasmic reticulum stress
- induced apoptosis
- signaling pathway
- oxidative stress
- binding protein
- squamous cell carcinoma
- ejection fraction
- type diabetes
- protein protein
- small molecule
- small cell lung cancer
- cardiovascular disease
- diabetic rats
- high resolution
- endothelial cells
- mass spectrometry
- simultaneous determination
- prognostic factors
- drug induced
- high glucose
- peritoneal dialysis