Comprehensive circular RNA profiling reveals that hsa_circ_0001368 is involved in growth hormone-secreting pituitary adenoma development

May 12, 2020Brain research bulletin

Detailed circular RNA analysis shows hsa_circ_0001368 may be linked to growth hormone tumor development in the pituitary gland

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Abstract

A total of 1938 circular RNAs were found to be upregulated in growth hormone-secreting pituitary adenoma (GHPA) compared to normal controls.

GHPA accounts for approximately 20% of all pituitary adenoma cases and is associated with serious health complications.
Gene Ontology and KEGG analyses revealed that target genes related to the upregulated circRNAs are enriched in the mTOR and Wnt signaling pathways.
Among the differentially expressed circRNAs, hsa_circ_0001368 was specifically upregulated in GHPA and correlated with tumor invasiveness and serum GH levels.
Knockdown of hsa_circ_0001368 in GHPA primary culture cells significantly inhibited their proliferation, invasion, and GH secretion.
hsa_circ_0001368 showed a significant positive correlation with the pituitary-specific transcription factor Pit-1.

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Growth hormone-secreting pituitary adenoma (GHPA) represents about 20% of all histological subtypes of pituitary adenoma (PA), which may result in serious complications and shortened lifespan via growth-hormone (GH) hypersecretion. To date, no biomarkers of early diagnosis or therapeutic targets for GHPA treatment have yet been found. Recently, growing evidence has indicated that circular RNAs (circRNAs) are critical for the development and progression of numerous diseases, including cancers; however, their role in the pathogenesis of GHPA has not been reported. Here, we revealed the expression profile of circRNAs in GHPA using a circRNA microarray, and found 1938 circRNAs were upregulated and 1601 circRNAs were downregulated in GHPA versus normal control. Then the ten most up-regulated circRNAs were selected for the mapping of a circRNA-miRNA-target gene interaction network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses further indicate that target genes were mostly enriched in the mTOR and the Wnt signaling pathway. Among these differentially expressed circRNAs, hsa_circ_0001368 was verified significant up-regulated by qRT-PCR, which was specific up-regulated in GHPA and correlated with the invasiveness and serum GH level of GHPA; functional studies indicated that knockdown of hsa_circ_0001368 significantly inhibited the proliferation, invasion and GH secreting level of GHPA primary culture cells. Moreover, hsa_circ_0001368 had a significant positive correlation with the pituitary-specific transcription factor Pit-1. In conclusion, our study identified a wealth of candidate circRNAs involved in GHPA and proposed that hsa_circ_0001368 may represent a novel potential biomarker and therapeutic target of GHPA.

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Comprehensive circular RNA profiling reveals that hsa_circ_0001368 is involved in growth hormone-secreting pituitary adenoma development

Abstract

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