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Long Non-Coding RNA H19 Expression Correlates with Autophagy Process in Adrenocortical Carcinoma.
- Source :
-
Cancer investigation [Cancer Invest] 2022 Mar; Vol. 40 (3), pp. 254-267. Date of Electronic Publication: 2021 Nov 16. - Publication Year :
- 2022
-
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 a utophagy 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.
- Subjects :
- Adolescent
Adrenal Cortex Neoplasms drug therapy
Adrenal Cortex Neoplasms pathology
Adrenocortical Carcinoma drug therapy
Adrenocortical Carcinoma pathology
Adult
Aged
Aged, 80 and over
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors analysis
Beclin-1 analysis
Cell Line, Tumor
Female
Histone Deacetylase Inhibitors therapeutic use
Humans
Male
Middle Aged
Panobinostat therapeutic use
RNA, Long Noncoding analysis
Young Adult
Adrenal Cortex Neoplasms genetics
Adrenocortical Carcinoma genetics
Autophagy physiology
RNA, Long Noncoding physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1532-4192
- Volume :
- 40
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Cancer investigation
- Publication Type :
- Academic Journal
- Accession number :
- 34726962
- Full Text :
- https://doi.org/10.1080/07357907.2021.2001483