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Effect of FTO-KD or FTO-OE on gene expression in GH3 cell line

ABSTRACT: Growth hormone-secreting pituitary adenomas account for approximately 10% of endocrine pituitary tumors and are pathologically classified into densely granulated adenomas (DGGH) and sparsely granulated adenomas (SGGH). m6A has been reported to play an important role in tumorigenesis and development, but its potential role in the pathogenesis of these two subtypes has not yet been thoroughly investigated. Consequently, we performed MeRIP-seq analysis of pituitary adenomas and the GH3 cell line. We observed that the expression of FTO was significantly increased in SGGH, leading to a reduction in m6A modification and a disruption of desmosome organization.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE269044 | GEO | 2024/09/25

REPOSITORIES: GEO

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Project description:Pituitary adenomas are common benign neoplasms giving rise to disorders of growth, reproductive function and cortisol production. Although recently determined to be monoclonal, very little is known about the mechanisms regulating the development of pituitary hyperplasia and neoplasia in humans. Surgical resection is the treatment of choice for most symptomatic pituitary adenomas. The goal of surgery is the complete removal of the tumor and the success of surgery is strongly affected by the presence of local invasion. However, complete tumor removal is unlikely when there is extensive local invasion. Identifying genes that control the invasiveness and recurrence of this class of tumors will provide therapeutic targets for this class of tumors. We will determine the expression pattern of genes in recurrent and invasive and pituitary adenomas and compare those to non-invasive and non-recurrent tumors. We hypothesize that the differential expression and activation of a number of genes affect pituitary adenoma recurrence and invasiveness. Rationale: Preliminary result showed a differential expression of novel PKC isozymes in non-invasive and invasive pituitary adenomas. PMA, an activator of both novel and classical PKC isozymes increased the expression of gelatinase A (MMP-2) mRNA in human pituitary adenoma cell line. This result raises a fundamental question as to the functional role of novel PKC isozymes and proteases in the invasive phenotype of pituitary adenomas. The primary component of this Specific Aim is to determine whether specific genes are differentially expressed in recurrent or invasive adenomas when compared with control non-invasive tumors. Tissue specimens from non-invasive and invasive (dural invasion based microscopic examination) and recurrent vs non-recurrent tumors will be used for microarray analysis. Frozen pituitaryspecimens will be collected and total RNA extracted with TriZol reagent. We will provide total RNA (10 ug) from non-invasive, invasive, reoccurred and non-occurrent pituitary adenomas. Keywords: other

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Effect of FTO-KD or FTO-OE on gene expression in GH3 cell line

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