LncRNA LINC00473 is involved in the progression of invasive pituitary adenoma by upregulating KMT5A via ceRNA-mediated miR-502-3p evasion.

Long noncoding RNAs (lncRNAs) and their crosstalks with other RNAs have been revealed to be closely related to tumorigenesis and development, but their role in invasive pituitary adenoma (IPA) remains largely unclear. In our study, LINC00473 was identified as the most upregulated lncRNA in IPA by whole transcriptome RNA sequencing (RNA-Seq). Further, its related signaling pathway LINC00473/miR-502-3p/KMT5A was obtained by constructing a competing endogenous RNA (ceRNA) regulatory network. Their expression in IPA and non-invasive pituitary adenoma (NIPA) tissues was verified by qRT-PCR. Then the effects and mechanisms of LINC00473 and its ceRNA network on the proliferation of pituitary adenoma (PA) cells were confirmed by gene overexpression or silencing techniques combined with CCK-8 assay, EdU staining, flow cytometry assay, and double luciferase reporter gene assay in PA cell lines AtT-20 and GT1-1 in vitro and in a xenograft model in vivo. LINC00473 is overexpressed in IPA and can promote PA cells proliferation. Mechanistically, overexpression of LINC00473 restricts miR-502-3p through the ceRNA mechanism, upregulates KMT5A expression, and promotes the expression of cyclin D1 and CDK2, which is conducive to the cell cycle process, thereby promoting the proliferation of PA cells, involving IPA progression.

Risk factors for the incidence of apoplexy in pituitary adenoma: a single-center study from southwestern China.

BACKGROUND: Although the incidence and clinical manifestations of pituitary apoplexy were reported by a few researches, the results are not consistent. This study aimed to explore the risk factors associated with an incidence of apoplexy in pituitary adenomas. METHODS: The clinical information of 843 patients with pituitary adenoma from the Department of Neurological Surgery, 1st Affiliated Hospital of Kunming Medical University, was reviewed. The incidence, clinical manifestation, and potential risk factors for pituitary apoplexy were analyzed by a case-control study. RESULTS: In total, 121 patients (14.4%) with macroadenoma were suffered from pituitary apoplexy. Headache, vomiting, and visual impairment are the top 3 symptoms for the pituitary apoplexy.Logistic regression results showed that the hypertension(hypertension vs non-hypertension OR = 2.765, 95%CI:1.41~5.416), tumor type (negative staining vs. positive staining, OR = 1.501, 95%CI:1.248~5.235), and tumor size (diameter > 2 cm vs. diameter ≤ 2 cm, OR = 3.952, 95%CI:2.211~7.053) are independent factors associated with pituitary apoplexy. CONCLUSION: Our results indicate that the risk factors for the incidence of pituitary apoplexy depend mainly on properties of the tumor itself (tumor size and pathologic type) and the blood pressure of patients.

Hypoxia promotes proliferation of pituitary adenomas by HIF-1α/ALKBH5 signaling in vitro.

Hypoxia is a common phenomenon in pituitary adenomas (PAs). The role and mechanism of hypoxia in the PAs remains elusive. This work aimed to explore the effect of hypoxia on PAs in vitro. PA cells GT1-1 were cultured and treated under hypoxic condition. Cell proliferation assay showed the proliferation of PA cells was increased significantly by hypoxia treatment, with a peak at 12 hours. qPCR and western blot indicated that the expression of HIF-1α, ALKBH5, and Nanog were elevated by hypoxia stimuli. In conclusion, our funding demonstrated that hypoxia could increase Nanog expression through HIF-1α/ALKBH5 signaling, thereby promoting the proliferation of PA cells.

Analysis of whole genome-wide microRNA transcriptome profiling in invasive pituitary adenomas and non-invasive pituitary adenomas.

BACKGROUND: Dysregulation of microRNAs (miRNAs) plays a critical role during the occurrence and progress of pituitary adenomas (PAs). However, the roles of miRNAs in the invasiveness of PA are poorly understood. This study aims to more comprehensively and specific define the relationship between altered miRNA and PA invasion. METHODS: The differential expression of miRNAs (DEMs) between invasive PAs (IPAs) and non-invasive PAs (NPAs) was explored by RNA sequencing and which functions were analyzed by gene ontology (GO) as well as Kyoto Encyclopedia of Genes and Genomes (KEGG). The miRNA-mRNA network was predicted with bioinformatics. RESULTS: We identified 31 upregulated miRNAs and 24 downregulated miRNAs in IPAs compared with NPAs. GO analysis and KEGG pathway analysis showed the DEMs were mainly associated with cell proliferation and cell cycle pathway. In addition, on the count of predicted miRNA-mRNA network, two hub miRNAs were identified. CONCLUSIONS: Our results demonstrate the miRNA-mRNA network in detail, which suggest that miRNA may be a promising target in diagnosis and therapy for IPAs.