MicroRNA-524-5p Functions as a Tumor Suppressor in a Human Pituitary Tumor-Derived Cell Line

Abstract

Clinical nonfunctional pituitary adenomas (NFAs) account for about 40% of pituitary adenomas with almost no clinically relevant hormonal symptoms. Increasing evidence shows that many microRNAs are involved in the development and progression of pituitary adenomas. MicroRNA-524-5p (miR-524-5p) has been reported to cause characteristic alterations in various tumors. However, the functional importance of miR-524-5p in NFAs remains unknown. The aim of this study was to explore the effects of overexpressing miR-524-5p on the proliferation, migration, invasion, and tumorigenicity of pituitary-derived folliculostellate (PDFS) cells using lentiviral transfection. Interestingly, the results showed that overexpressing miR-524-5p downregulated pituitary tumor-transforming gene 1 (PTTG1) binding factor (PBF) expression at both mRNA and protein levels and significantly attenuated cell proliferation, clonogenicity, migration, and invasion in vitro. Moreover, enhancing miR-524-5p blocked tumor growth in a nude mouse xenograft model in vivo. These findings suggest that miR-524-5p appears to play a critical role in the regulation of biological properties of PDFS cells, and may represent a potential therapeutic target for NFAs.

MicroRNAs and Target Genes in Pituitary Adenomas

“…These miRNAs decreased Wee1 protein expression and inhibited HeLa cell proliferation [71]. Studies conducted by our research group have found overexpressing miR-524-5p [72] downregulated PTTG1-binding factor (PBF) expression and regulated the biological properties of PDFS(pituitary tumor-derived folliculostellate cell). This could be noted as a potential therapeutic target for non-functioning pituitary adenomas.…”

MiRNAs as Noninvasive Biomarkers and Therapeutic Agents of Pituitary Adenomas

“…Whether or not other miRNAs regulate PA pathogenesis by similarly targeting tumor oncogenes or tumor suppressor genes needs further study. A brief summary of differentially expressed miRNAs in PAs with their targets and implications is tabulated in Table 1 [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ].…”

Mouse models of endocrine tumors

“…Indeed, in recent years, mice xenografts have been widely used to characterize the responses to drugs currently prescribed for these pathologies as lanreotide (Ning et al 2009), thiazolidinediones (Mannelli et al 2010), bromocriptine and/or cabergoline (Lin et al 2017) or to alternative therapies such as metformin , histone deacetylase inhibitor SAHA (Lu et al 2017), Liquiritigenin (Wang et al 2014), Triptolide (Li et al 2017) or Bafilomycin A1 (McSheehy et al 2003), which have been shown to exhibit antitumoral roles in these pathologies. Likewise, PAs xenograft models have also been used to characterize the function of different pathways, genes and relevant mutations in several types of PAs, as Fgfr4 in intracranial xenograft mouse models (Ezzat et al 2006, Jalali et al 2016, inactivating mutations of Pit-1 (Roche et al 2012), overexpression of Lrig1 (Cheng et al 2016) or Meg3 (Chunharojrith et al 2015), persistent activation of the Ras/MAPK pathway (Booth et al 2014), antitumoral actions of miR-524-5p (Zhen et al 2017) and role of RSUME in PTTG protein stabilization (Fuertes et al 2018). Finally, PDX models have been sparsely implemented in the case of PAs.…”