MicroRNA 375 Mediates the Signaling Pathway of Corticotropin-releasing Factor (CRF) Regulating Pro-opiomelanocortin (POMC) Expression by Targeting Mitogen-activated Protein Kinase 8

Zhang, Nan; Lin, Jun-Kai; Chen, Juan; Liu, Xiongfei; Liu, Jiali; Luo, Hanpeng; Li, Yueqin; Cui, Sheng

doi:10.1074/jbc.m112.425504

Cited by 64 publications

(60 citation statements)

References 47 publications

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“…At first glance this result seems to vary from our observations. However, several studies have reported that miR-375 acts not as a positive regulator of cell proliferation but rather as a negative modulator (24,(34)(35)(36). At least two scenarios could account for this apparent divergence.…”

Section: Discussionmentioning

confidence: 99%

Maternal Protein Restriction Leads to Pancreatic Failure in Offspring: Role of Misexpressed MicroRNA-375

et al. 2014

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The intrauterine environment of the fetus is a preeminent actor in long-term health. Indeed, mounting evidence shows that maternal malnutrition increases the risk of type 2 diabetes (T2D) in progeny. Although the consequences of a disturbed prenatal environment on the development of the pancreas are known, the underlying mechanisms are poorly defined. In rats, restriction of protein during gestation alters the development of the endocrine pancreas and favors the occurrence of T2D later in life. Here we evaluate the potential role of perturbed microRNA (miRNA) expression in the decreased b-cell mass and insulin secretion characterizing progeny of pregnant dams fed a low-protein (LP) diet. miRNA profiling shows increased expression of several miRNAs, including miR-375, in the pancreas of fetuses of mothers fed an LP diet. The expression of miR-375 remains augmented in neoformed islets derived from fetuses and in islets from adult (3-month-old) progeny of mothers fed an LP diet. miR-375 regulates the proliferation and insulin secretion of dissociated islet cells, contributing to the reduced b-cell mass and function of progeny of mothers fed an LP diet. Remarkably, miR-375 normalization in LP-derived islet cells restores b-cell proliferation and insulin secretion. Our findings suggest the existence of a developmental memory in islets that registers intrauterine protein restriction. Hence, pancreatic failure after in utero malnutrition could result from transgenerational transmission of miRNA misexpression in b-cells.

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Section: Discussionmentioning

confidence: 99%

Maternal Protein Restriction Leads to Pancreatic Failure in Offspring: Role of Misexpressed MicroRNA-375

et al. 2014

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“…Egy másik tanulmány-ban az egér központi idegrendszerének különböző részeit vizsgálva sikerült agyalapimirigyre specifikus miRNS-eket azonosítani [22]. Amellett, hogy a miRNSeknek az emberben is fontos szerepük van a normál mirigy fejlődésében [19,23,24] és hormontermelésében [25][26][27][28][29][30][31], az elmúlt években egyre több humán vizsgálat támasztja alá azt is, hogy részt vehetnek az adenomák kialakulásában és növekedésében [32][33][34][35].…”

Section: Mirns-expressziós Eltérések Az Agyalapimirigy-daganatokbanunclassified

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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“…miRNAs are critical regulators in pituitary development, it is reported that mmu-miR-26b targets lymphoid enhancer factor 1 (LEF1), which up-regulates PIT1 and GH expressions [42]. A highly expressed miRNA in the pituitary gland, mmu-miR-375, is reported to regulate the signaling pathway of CRF and POMC expressions by targeting mitogen-activated protein kinase-8 (MAP3K8) [41]. In our previous study, we detected a large number of porcine miRNAs by using a combination of microarray analysis and Solexa sequencing [21], and differentially expressed miRNAs after GNRH treatment were revealed by miRNA microarray [39].…”

Section: Introductionmentioning

confidence: 99%

Alteration of the miRNA expression profile in male porcine anterior pituitary cells in response to GHRH and CST and analysis of the potential roles for miRNAs in regulating GH

Qi¹,

Xi²,

Ye³

et al. 2015

Growth Hormone & IGF Research

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MicroRNA 375 Mediates the Signaling Pathway of Corticotropin-releasing Factor (CRF) Regulating Pro-opiomelanocortin (POMC) Expression by Targeting Mitogen-activated Protein Kinase 8

Cited by 64 publications

References 47 publications

Maternal Protein Restriction Leads to Pancreatic Failure in Offspring: Role of Misexpressed MicroRNA-375

Maternal Protein Restriction Leads to Pancreatic Failure in Offspring: Role of Misexpressed MicroRNA-375

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

Alteration of the miRNA expression profile in male porcine anterior pituitary cells in response to GHRH and CST and analysis of the potential roles for miRNAs in regulating GH

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