miRNA-199a-5p functions as a tumor suppressor in prolactinomas

Wang, Jichao; Guo, Jing; Fei, Wang; Cao, Lei; Liu, Qian; Feng, J. H.; Wang, Hongyun; Gao, Hua; Zhang, Yazhou

doi:10.1515/chem-2019-0036

Cited by 4 publications

(1 citation statement)

References 36 publications

(42 reference statements)

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“…To functional prove miR-199a-5p effect, the authors demonstrated that overexpression of miR-199a-5p suppressed cell differentiation and invasive behaviour of pituitary tumour cells. Interestingly, the miR-199a-5p overexpression downregulated SAT1 protein and mRNA levels (Table 1 ) [ 121 ].…”

Section: Noncoding Rna Regulation Of Polyamine Metabolism In Cancermentioning

confidence: 99%

Unveiling the hidden players: noncoding RNAs orchestrating polyamine metabolism in disease

Rossi,

Fiorucci,

Mariottini

et al. 2024

Cell Biosci

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Polyamines (PA) are polycations with pleiotropic functions in cellular physiology and pathology. In particular, PA have been involved in the regulation of cell homeostasis and proliferation participating in the control of fundamental processes like DNA transcription, RNA translation, protein hypusination, autophagy and modulation of ion channels. Indeed, their dysregulation has been associated to inflammation, oxidative stress, neurodegeneration and cancer progression. Accordingly, PA intracellular levels, derived from the balance between uptake, biosynthesis, and catabolism, need to be tightly regulated. Among the mechanisms that fine-tune PA metabolic enzymes, emerging findings highlight the importance of noncoding RNAs (ncRNAs). Among the ncRNAs, microRNA, long noncoding RNA and circRNA are the most studied as regulators of gene expression and mRNA metabolism and their alteration have been frequently reported in pathological conditions, such as cancer progression and brain diseases. In this review, we will discuss the role of ncRNAs in the regulation of PA genes, with a particular emphasis on the changes of this modulation observed in health disorders.

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Section: Noncoding Rna Regulation Of Polyamine Metabolism In Cancermentioning

confidence: 99%

Unveiling the hidden players: noncoding RNAs orchestrating polyamine metabolism in disease

Rossi,

Fiorucci,

Mariottini

et al. 2024

Cell Biosci

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The emerging role of miRNAs in pituitary adenomas: From molecular signatures to diagnostic potential

Doghish,

El-Sayyad,

Abdel Mageed

et al. 2024

Experimental Cell Research

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MicroRNA-Mediated Drug Repurposing Unveiled Potential Candidate Drugs for Prolactinoma Treatment

et al. 2021

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Introduction: Prolactinomas, also called lactotroph adenomas, are the most encountered type of hormone-secreting pituitary neuroendocrine tumors (PitNET) in the clinic. The preferred first-line therapy is a medical treatment with dopamine agonists (DA), mainly cabergoline, to reduce serum prolactin levels, tumor volume, and mass effect. However, in some cases, patients have displayed DA-resistance with aggressive tumor behavior or are faced with recurrence after drug withdrawal. Also, currently used therapeutics have notorious side effects and impair the life quality of the patients. Methods: Since the amalgamation of clinical and laboratory data besides tumor histopathogenesis and transcriptional regulatory features of the tumor emerge to exhibit essential roles in the behavior and progression of prolactinomas, in this work, we integrated mRNA and microRNA (miRNA) level transcriptome data that exploit disease-specific signatures in addition to biological and pharmacological data to elucidate a rational prioritization of pathways and drugs in prolactinoma. Results: We identified eight drug candidates through drug repurposing based on mRNA-miRNA level data integration and evaluated their potential through in vitro assays in the MMQ cell line. Seven re-purposed drugs including 5-flourocytosine, nortriptyline, neratinib, puromycin, taxifolin, vorinostat, and zileuton were proposed as potential drug candidates for the treatment of prolactinoma. We further hypothesized possible mechanisms of drug action on MMQ cell viability through analyzing PI3K/Akt signaling pathway and cell cycle arrest via flow cytometry and western blotting. Discussion: We presented the transcriptomic landscape of prolactinoma through miRNA and mRNA level data integration and proposed repurposed drug candidates based on this integration. We validated our findings through testing cell viability, cell cycle phases, and PI3K/Akt protein expressions. Effects of the drugs on cell cycle phases and inhibition of PI3K/Akt pathway by all drugs gave us promising output for further studies using these drugs in the treatment of prolactinoma. This is the first study that reports miRNA-mediated repurposed drugs for prolactinoma treatment via in vitro experiments.

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miRNA-199a-5p functions as a tumor suppressor in prolactinomas

Cited by 4 publications

References 36 publications

Unveiling the hidden players: noncoding RNAs orchestrating polyamine metabolism in disease

Unveiling the hidden players: noncoding RNAs orchestrating polyamine metabolism in disease

The emerging role of miRNAs in pituitary adenomas: From molecular signatures to diagnostic potential

MicroRNA-Mediated Drug Repurposing Unveiled Potential Candidate Drugs for Prolactinoma Treatment

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