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Exploratory Circular RNA Profiling in Adrenocortical Tumors.

Péter István Turai1,2,3, Gábor Nyirő1,2,3,4, Katalin Borka5

  • 1Department of Endocrinology, ENS@T Research Center of Excellence, Faculty of Medicine, Semmelweis University, H-1083 Budapest, Hungary.

Cancers
|September 9, 2022
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Summary

Circular RNAs (circRNAs) show altered expression in adrenocortical tumors. Only circPHC3 was significantly overexpressed in both adrenocortical adenoma (ACA) and carcinoma (ACC) compared to normal tissue, suggesting potential diagnostic relevance.

Keywords:
RT-qPCRadrenal tissueadrenocortical adenomaadrenocortical carcinomabiomarkercircular RNAexpressionmicroRNAnext-generation sequencing

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Area of Science:

  • Endocrinology
  • Molecular Biology
  • Genomics

Background:

  • Differentiating adrenocortical adenoma (ACA) from carcinoma (ACC) is diagnostically challenging.
  • Circular RNAs (circRNAs), a class of non-coding RNAs, are increasingly recognized for their roles in tumorigenesis.

Purpose of the Study:

  • To investigate circRNA expression profiles in adrenocortical tumors using next-generation sequencing (NGS).
  • To validate differential circRNA expression and explore potential microRNA sponging interactions in ACA and ACC.

Main Methods:

  • NGS was employed for circRNA profiling in formalin-fixed, paraffin-embedded (FFPE) tissues (8 ACC, 8 ACA, 8 normal adrenal cortices - NAC).
  • Bioinformatics tools (CIRI2, CircExplorer2, AutoCirc) identified circRNAs.
  • RT-qPCR validated the expression of top differentially expressed circRNAs in an independent cohort (10 ACC, 8 ACA, 8 NAC).
  • In silico analysis predicted microRNA sponging interactions, with subsequent RT-qPCR assays.

Main Results:

  • NGS revealed significantly differentially expressed circRNAs between tumor types and normal tissue.
  • Only circPHC3 was consistently and significantly overexpressed in both ACC and ACA compared to NAC upon RT-qPCR validation.
  • Observed microRNA expression changes did not fully support the predicted sponging hypothesis for the studied circRNAs.

Conclusions:

  • This study is the first to explore circRNA expression in adrenocortical tumors.
  • circPHC3 warrants further investigation for its potential as a diagnostic biomarker in adrenocortical tumors.
  • Additional research is needed to elucidate the biological functions and diagnostic utility of circRNAs in adrenocortical tumorigenesis.