The Molecular Pathogenesis of Pituitary Adenomas: An Update

Jiang, Xiaobing; Zhang, Xun

doi:10.3803/enm.2013.28.4.245

Cited by 54 publications

(49 citation statements)

References 75 publications

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“…[11,14,45] Thus far, investigations characterizing the inappropriate expression of miRNA in the genesis of pituitary adenomas has already led to the identification of subtype-specific miRNA profiles [46,47,16], identification of miRNA that show correlations with tumour size [40] or are predictive of tumor sensitivity and or response to therapeutic interventions. [47,16] and have been subject to recent and extensive review, [48][49][50][51]. Still more recent studies have focused on the target transcripts for these miRNA.…”

Section: Discussionmentioning

confidence: 99%

Epidrug mediated re-expression of miRNA targeting the HMGA transcripts in pituitary cells

et al. 2015

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Section: Discussionmentioning

confidence: 99%

Epidrug mediated re-expression of miRNA targeting the HMGA transcripts in pituitary cells

et al. 2015

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“…Changes in the expression or function of several cytokines and growth factors have been described to participate in pituitary adenoma development (Perez-Castro et al 2012), as it is well known that normal pituitary cells are under the auto/paracrine action of these factors. Altered levels of transforming growth factor alpha and beta protein families, epidermal growth factor, fibroblast growth factor family, bone morphogenetic protein 4 and IL-6/ gp130 family, have been observed in pituitary tumors (Jones et al 1994, Dworakowska & Grossman 2012, Perez-Castro et al 2012, Jiang & Zhang 2013. It was described that matrix metalloproteinase, secreted by pituitary cells, contribute to the control of cell proliferation during tumorigenesis also (Paez-Pereda et al 2005).…”

Section: Pathophysiological Role Of Il-6 In the Pituitarymentioning

confidence: 99%

Programmed cell senescence: role of IL-6 in the pituitary

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2017

Journal of Molecular Endocrinology

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IL-6 is a pleiotropic cytokine with multiple pathophysiological functions. As a key factor of the senescence secretome, it can not only promote tumorigenesis and cell proliferation but also exert tumor suppressive functions, depending on the cellular context. IL-6, as do other cytokines, plays important roles in the function, growth and neuroendocrine responses of the anterior pituitary gland. The multiple actions of IL-6 on normal and adenomatous pituitary function, cell proliferation, angiogenesis and extracellular matrix remodeling indicate its importance in the regulation of the anterior pituitary. Pituitary tumors are mostly benign adenomas with low mitotic index and rarely became malignant. Premature senescence occurs in slow-growing benign tumors, like pituitary adenomas. The dual role of IL-6 in senescence and tumorigenesis is well represented in pituitary tumor development, as it has been demonstrated that effects of paracrine IL-6 may allow initial pituitary cell growth, whereas autocrine IL-6 in the same tumor triggers senescence and restrains aggressive growth and malignant transformation. IL-6 is instrumental in promotion and maintenance of the senescence program in pituitary adenomas.

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“…Egyedül prolactinomákban igazolható a HMGA fokozott kifejeződéséért felelős kromoszómael-térés (12-es triszómia). A többi adenomatípusban a gé-nek fokozott expresszióját egyelőre egyedül a miRNSeknek tulajdonítják [9]. Igazolták a let-7 miRNS és a HMGA2 expressziója közötti negatív korrelációt.…”

Section: A Mirns-ek áLtal Szabályozott Hmga-fehérjék Komplex Szerepe unclassified

“…Mai tudásunk alapján az agyalapimirigy-daganatok monoklonális tumorok, ennek ellenére jóindulatúak, lassan növekednek, és csak nagyon ritkán képeznek áttétet, bár alkalmanként lokálisan invazív viselkedést mutatnak [9]. A neuroendokrin tumorokban vagy egyéb szolid tumorokban megtalálható gyakori génmutációk (PKC, RAS, P53, RB, KRAS, EGFR, VEGFR) nem jellemzőek rájuk.…”

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A mikro-RNS-ek szerepe az agyalapimirigy-daganatok tumorbiológiájában

et al. 2018

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A mikro-RNS-ek rövid, egyszálú RNS-molekulák, melyek szabályozó szerepüket más gének poszttranszkripcionális módosítása révén fejtik ki. A humán fehérjéket kódoló gének nagyjából 30%-a miRNS-ek szabályozása alatt is áll, aminek révén olyan alapvető folyamatokat befolyásolnak, mint a sejtosztódás, -differenciálódás és sejthalál. Számos daganattípussal kapcsolatban írták már le a megváltozott miRNS-expressziós mintázatot, és egyre több közlemény veti fel, hogy a miRNS-ek, mint terápiás célpontok is szóba jöhetnek. A csökkent expressziójú miRNS-ek adásán, illetve az emelkedett expressziót mutató miRNS-ek gátlásán keresztül nem csak egyetlen gén, hanem egész jelátviteli útvonalak befolyásolása is lehetővé válhat. Az agyalapimirigy-daganatok a leggyakoribb intracranialis tumorok közé tartoznak. Gyakoriságuk ellenére a sporadikusan előforduló adenomák kialakulásának molekuláris mechanizmusa még kevéssé van feltárva. Az utóbbi években egyre több bizonyíték utal arra, hogy a mikro-RNS-eknek fontos szerepük van az adenomagenezisben. Összefoglalónkban az agyalapimirigy-adenomákban leírt miRNS-ek szerepét kíván-juk bemutatni, valamint felvázolni a miRNS-ekhez kapcsolódó terápiás lehetőségeket. Orv Hetil. 2018; 159(7): 252-259. Kulcsszavak: mikro-RNS, agyalapimirigy-adenoma, biomarkerThe role of miRNAs in the pathogenesis of pituitary adenomas MicroRNAs (miRNAs) are short, single stranded RNA molecules which play regulatory roles through posttranscriptional regulation of their target genes. Based on our current knowledge, more than 30% of the human protein-coding genes are regulated by miRNAs, hence influencing basic cellular mechanisms including cell proliferation, differentiation and cell death. Differential miRNA expression pattern has been detected in many different types of tumors and, recently, several publications have referred to miRNAs as potential therapeutic targets. Through adjustment of miRNA levels by artificial miRNAs administration or miRNA inhibition, we can influence not only one target gene but also complex biological pathways. Pituitary adenoma is the second most frequent intracranial tumor. In spite of this, the molecular mechanism of the pituitary adenoma formation is not yet entirely revealed. Recently, more and more evidences have been found suggesting that miRNAs have an important role in pituitary adenoma pathogenesis. Here, we summarize the recent results related to this role and highlight the therapeutic potentials in pituitary adenomas.

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The Molecular Pathogenesis of Pituitary Adenomas: An Update

Cited by 54 publications

References 75 publications

Epidrug mediated re-expression of miRNA targeting the HMGA transcripts in pituitary cells

Epidrug mediated re-expression of miRNA targeting the HMGA transcripts in pituitary cells

Programmed cell senescence: role of IL-6 in the pituitary

A mikro-RNS-ek szerepe az agyalapimirigy-daganatok tumorbiológiájában

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