Long Non-Coding RNA H19 Expression Correlates with Autophagy Process in Adrenocortical Carcinoma

Abstract

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.

Keywords:

• H19
• autophagy
• deacetylase inhibitors
• adrenocortical carcinoma

Acknowledgments

The authors are thankful to Katrin Roth (Center for Tumor Biology and Immunology, Philipps University Marburg) for the microscopy advices and support, to Carmen Bollmann (Department of Visceral, Thoracic and Vascular Surgery, Philipps University Marburg) for the technical assistance, to Uwe Schlomann (Department of Visceral, Thoracic and Vascular Surgery, Philipps University Marburg) for reading the manuscript and his meaningful advices.

Author contributions

PD, KH conceived and designed the study. FR, SR, PD, AP performed the experiments. PD, FR, IM analyzed the data. PD, FR wrote and revised the manuscript. SW, KH, DKB provided study material, supervised and supported analyses and edited the manuscript. All authors critically reviewed the manuscript.

Disclosure statement

All authors declare no conflict of interest.