RPSAP52 lncRNA is overexpressed in pituitary tumors and promotes cell proliferation by acting as miRNA sponge for HMGA proteins

Long non-coding RNAs (lncRNAs) are emerging as fundamental players in cancer biology. Indeed, they are deregulated in several neoplasias and have been associated with cancer progression, tumor recurrence, and resistance to treatment, thus representing potential biomarkers for cancer diagnosis, progn...

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Published in:Journal of molecular medicine (Berlin, Germany) Germany), 2019-07, Vol.97 (7), p.1019-1032
Main Authors: D’Angelo, Daniela, Mussnich, Paula, Sepe, Romina, Raia, Maddalena, del Vecchio, Luigi, Cappabianca, Paolo, Pellecchia, Simona, Petrosino, Sara, Saggio, Serena, Solari, Domenico, Fraggetta, Filippo, Fusco, Alfredo
Format: Article
Language:English
Subjects:
Antisense therapy
Base Sequence
Binding Sites - genetics
Biomedical and Life Sciences
Biomedicine
Brain cancer
Brain tumors
Cancer
Cell cycle
Cell Cycle - genetics
Cell growth
Cell Line, Tumor
Cell proliferation
Cell Proliferation - genetics
Gene Expression Regulation, Neoplastic
HMGA Proteins - metabolism
Human Genetics
Humans
Internal Medicine
MicroRNAs - genetics
MicroRNAs - metabolism
miRNA
Molecular Medicine
Mutation - genetics
Original Article
Pituitary
Pituitary (anterior)
Pituitary gland
Pituitary Neoplasms - genetics
Pituitary Neoplasms - pathology
Prolactin
RNA, Long Noncoding - genetics
RNA, Long Noncoding - metabolism
Tumorigenesis
Tumors
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Summary:Long non-coding RNAs (lncRNAs) are emerging as fundamental players in cancer biology. Indeed, they are deregulated in several neoplasias and have been associated with cancer progression, tumor recurrence, and resistance to treatment, thus representing potential biomarkers for cancer diagnosis, prognosis, and therapy. In this study, we aimed to identify lncRNAs associated with pituitary tumorigenesis . We have analyzed the lncRNA expression profile of a panel of gonadotroph pituitary adenomas in comparison with normal pituitaries. Then, we focused on RPSAP52, a novel lncRNA antisense for the HMGA2 gene, whose overexpression plays a critical role in the development of pituitary adenomas. We report that RPSAP52 expression is highly upregulated in gonadotroph and prolactin-secreting pituitary adenomas, where it correlates with that of HMGA2, compared with normal pituitary tissues. Conversely, its expression showed a variable behavior in somatotroph adenomas. We also demonstrate that RPSAP52 enhances HMGA2 protein expression in a ceRNA-dependent way acting as sponge for miR-15a, miR-15b, and miR-16, which have been already described to be able to target HMGA2. Interestingly, RPSAP52 also positively modulates HMGA1, the other member of the High-Mobility Group A family. Moreover, functional studies indicate that RPSAP52 promotes cell growth by enhancing the G1-S transition of the cell cycle. The results reported here reveal a novel mechanism, based on the overexpression of the lncRNA RPSAP52, which contributes to pituitary tumorigenesis, and propose this lncRNA as a novel player in the development of these tumors. Key Messages RPSAP52 is overexpressed in pituitary adenomas. RPSAP52 increases HMGA protein levels. A ceRNA mechanism is proposed for the increased HMGA1/2 expression.
ISSN:0946-2716
1432-1440
DOI:10.1007/s00109-019-01789-7