PIT1 upregulation by HMGA proteins has a role in pituitary tumorigenesis

Palmieri, Dario; Valentino, Teresa; Martino, Ivana De; Esposito, Francesco; Cappabianca, Paolo; Wierinckx, Anne; Vitiello, Marianna; Lombardi, Gaetano; Colao, Annamaria; Trouillas, Jacqueline; Pierantoni, Giovanna Maria; Fedele, Monica

doi:10.1530/erc-11-0135

Cited by 32 publications

(20 citation statements)

References 58 publications

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“…Indeed, MEFs derived from transgenic mice overexpressing HMGA1P7 show a higher growth rate, and lower susceptibility to senescence with respect to the WT counterpart. Moreover, flow cytometry showed an increase of cells in S phase as expected given the ability of HMGA1 to increase the E2F1 activity [45]. …”

Section: Discussionmentioning

confidence: 94%

HMGA1pseudogenes as candidate proto-oncogenic competitive endogenous RNAs

et al. 2014

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The High Mobility Group A (HMGA) are nuclear proteins that participate in the organization of nucleoprotein complexes involved in chromatin structure, replication and gene transcription. HMGA overexpression is a feature of human cancer and plays a causal role in cell transformation. Since non-coding RNAs and pseudogenes are now recognized to be important in physiology and disease, we investigated HMGA1 pseudogenes in cancer settings using bioinformatics analysis. Here we report the identification and characterization of two HMGA1 non-coding pseudogenes, HMGA1P6 and HMGA1P7. We show that their overexpression increases the levels of HMGA1 and other cancer-related proteins by inhibiting the suppression of their synthesis mediated by microRNAs. Consistently, embryonic fibroblasts from HMGA1P7-overexpressing transgenic mice displayed a higher growth rate and reduced susceptibility to senescence. Moreover, HMGA1P6 and HMGA1P7 were overexpressed in human anaplastic thyroid carcinomas, which are highly aggressive, but not in differentiated papillary carcinomas, which are less aggressive. Lastly, the expression of the HMGA1 pseudogenes was significantly correlated with HMGA1 protein levels thereby implicating HMGA1P overexpression in cancer progression. In conclusion, HMGA1P6 and HMGA1P7 are potential proto-oncogenic competitive endogenous RNAs.

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Section: Discussionmentioning

confidence: 94%

HMGA1pseudogenes as candidate proto-oncogenic competitive endogenous RNAs

et al. 2014

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“…Moreover, the pituitary-specific transcription factor Pit-1 (POU domain, class 1, transcription factor 1) was found overexpressed in PAs from Hmga1b and Hmga2 transgenic mice. It has been also demonstrated that Pit-1 is positively regulated by HMGA protein and its overexpression positively correlates with that of HMGA also in human PAs (34). …”

Section: Hmga As Driver In the Development Of Human Pituitary Adenomasmentioning

confidence: 98%

Epigenetic Mechanisms Leading to Overexpression of HMGA Proteins in Human Pituitary Adenomas

D'Angelo

Esposito

2015

Front. Med.

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Overexpression of the high-mobility group A (HMGA)1 and HMGA2 proteins is a feature of all human pituitary adenoma (PAs) subtypes. However, amplification and/or rearrangement of the HMGA2 have been described in human prolactinomas, but rarely in other pituitary subtypes, and no genomic amplification of HMGA1 was detected in PAs. Here, we summarize the functional role of HMGA proteins in pituitary tumorigenesis and the epigenetic mechanisms contributing to HMGA overexpression in these tumors focusing on recent studies indicating a critical role of non-coding RNAs in modulating HMGA protein levels.

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“…Methylation or deletion of death associated protein kinase (DAPK), which serves the p19/p53 tumor suppressors, is associated with malignant tumors [51]. Finally, HMGA1b and HMGA2 have been shown in vivo to promote pituitary cell proliferation by increasing expression of PIT1, a transcription factor that aids in the normal development of the pituitary gland [52]. …”

Section: Pathophysiology and Clinical Manifestationsmentioning

confidence: 99%

Pituitary adenomas: historical perspective, surgical management and future directions

et al. 2015

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Pituitary adenomas are among the most common central nervous system tumors. They represent a diverse group of neoplasms that may or may not secrete hormones based on their cell of origin. Epidemiologic studies have documented the incidence of pituitary adenomas within the general population to be as high as 16.7%. A growing body of work has helped to elucidate the pathogenesis of these tumors. Each subtype has been shown to demonstrate unique cellular changes potentially leading to tumorigenesis. Surgical advancements over several decades have included microsurgery and the employment of the endoscope for surgical resection. These advancements increase the likelihood of gross-total resection and have resulted in decreased patient morbidity.

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PIT1 upregulation by HMGA proteins has a role in pituitary tumorigenesis

Cited by 32 publications

References 58 publications

HMGA1pseudogenes as candidate proto-oncogenic competitive endogenous RNAs

HMGA1pseudogenes as candidate proto-oncogenic competitive endogenous RNAs

Epigenetic Mechanisms Leading to Overexpression of HMGA Proteins in Human Pituitary Adenomas

Pituitary adenomas: historical perspective, surgical management and future directions

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