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.