Abstract
Background
Adrenocortical carcinoma is a rare endocrine cancer with poor overall survival. Linking
survival outcomes to a common target across multiple genomic datasets incorporating
microRNA-long non-coding RNA dysregulation have not been well described. We hypothesized
that a multi-database analysis of microRNA-long noncoding RNA-messenger RNA regulatory
networks associated with survival will identify novel biomarkers.
Methods
Significantly dysregulated genes or microRNA in adrenocortical carcinoma compared
to normal adrenal was identified from sequencing data for 260 human adrenocortical
carcinomas using GEO2R. The miRnet identified hub microRNA and genes and long noncoding
RNA and microRNA associated with survival genes. The R2 generated Kaplan-Meier curves.
The database miRTarBase linked genes associated with poor survival and dysregulated
microRNA.
Results
Analysis of genes and microRNAs differentially regulated in >50% of datasets revealed
75 genes and 12 microRNAs were upregulated, and 167 genes and 12 microRNAs were downregulated
(bonf. P < .05). Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed cell cycle,
P53 signaling, arachidonic acid and innate immune response, and PI3/Akt are altered
in adrenocortical carcinoma. A microRNA-target interaction network of differentially
regulated microRNAs identified upregulated miRNA107, 103a-3p and 27a-3p, 16-5p, and
downregulated 335-5p to have the highest degree of interaction with upregulated (ie,
TPX2, CDK1, BIRC5, PRC1, CCNB1, GINS1) and downregulated (ie, RSPO3, NR2F1, TLR4,
HOXA5, USP53, SLC16A9) hub genes as well as hub long noncoding RNAs XIST, NEAT1, KCNQ1OT1,
and PAX8-AS1. Survival analysis revealed that the hub genes are associated with poor
overall survival (P < .05) of adrenocortical carcinoma in the Cancer Genome Atlas data.
Conclusion
A messenger RNA–microRNA–long noncoding RNA network analysis identified the BIRC5-miR335-5p-PAX8-AS1
network as one that was associated with poor overall survival in adrenocortical carcinoma,
warranting further validation as a potential therapeutic target.
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References
- Adrenocortical carcinoma.Endocr Rev. 2014; 35: 282-326
- Clinical review: adrenocortical carcinoma: clinical update.J Clin Endocrinol Metab. 2006; 91: 2027-2037
- An eleven-year experience with adrenocortical carcinoma.Surgery. 1992; 112 (discussion 70–1): 963-970
- Longitudinal patterns of recurrence in patients with adrenocortical carcinoma.Surgery. 2019; 165: 186-195
- Adrenocortical carcinoma: clinical outcomes and prognosis of 330 patients at a tertiary care center.Eur J Endocrinol. 2013; 169: 891-899
- European Society of Endocrinology Clinical Practice Guidelines on the management of adrenocortical carcinoma in adults, in collaboration with the European Network for the Study of Adrenal Tumors.Eur J Endocrinol. 2018; 179: G1-G46
- Efficacy of the EDP-M scheme plus adjunctive surgery in the management of patients with advanced adrenocortical carcinoma: the Brescia experience.Cancers (Basel). 2020; 12: 941
- Adrenocortical carcinoma: current treatment options.Curr Opin Oncol. 2021; 33: 16-22
- Regulation of microRNA function in animals.Nat Rev Mol Cell Biol. 2019; 20: 21-37
- MicroRNA biogenesis pathways in cancer.Nat Rev Cancer. 2015; 15: 321-333
- MicroRNA therapeutics: towards a new era for the management of cancer and other diseases.Nat Rev Drug Discov. 2017; 16: 203-222
- The role of microRNAs in the pathophysiology of adrenal tumors.Mol Cell Endocrinol. 2017; 456: 36-43
- Adrenocortical carcinoma - towards genomics guided clinical care.Nat Rev Endocrinol. 2019; 15: 548-560
- Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources.Nat Protoc. 2009; 4: 44-57
- Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists.Nucleic Acids Res. 2009; 37: 1-13
Amsterdam University Medical Centers. R2: genomics analysis and visualization platform. http://r2.amc.nl. Accessed 5 June 2022.
- Cancer therapeutics using survivin BIRC5 as a target: what can we do after over two decades of study?.J Exp Clin Cancer Res. 2019; 38: 368
- Abrogation of TLR4 and CD14 expression and signaling in human adrenocortical tumors.J Clin Endocrinol Metab. 2010; 95: E421-E429
- An NR2F1-specific agonist suppresses metastasis by inducing cancer cell dormancy.J Exp Med. 2022; 219e20210836
- Identification of biomarkers of adrenocortical carcinoma using genomewide gene expression profiling.Arch Surg. 2008; 143 (discussion 846): 841-846
- Homeobox A5 activates p53 pathway to inhibit proliferation and promote apoptosis of adrenocortical carcinoma cells by inducing Aldo-Keto reductase family 1 member B10 expression.Bioengineered. 2021; 12: 1964-1975
- USP53 activated by H3K27 acetylation regulates cell viability, apoptosis, and metabolism in esophageal carcinoma via the AMPK signaling pathway.Carcinogenesis. 2022; 43: 349-359
- USP53 promotes apoptosis and inhibits glycolysis in lung adenocarcinoma through FKBP51-AKT1 signaling.Mol Carcinog. 2020; 59: 1000-1011
- Functions and targets of miR-335 in cancer.Onco Targets Ther. 2021; 14: 3335-3349
- Overexpression of PAX8-AS1 inhibits malignant phenotypes of papillary thyroid carcinoma cells via miR-96-5p/PKN2 axis.Int J Endocrinol. 2021; 20215499963
Article info
Publication history
Published online: October 03, 2022
Accepted:
August 9,
2022
Footnotes
Chitra Subramanian and Mark S. Cohen contributed equally.
Identification
Copyright
© 2022 Published by Elsevier Inc.
