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侵袭性生长激素分泌型垂体腺瘤中的潜在生物标志物和 lncRNA-mRNA 调控网络。

Potential biomarkers and lncRNA-mRNA regulatory networks in invasive growth hormone-secreting pituitary adenomas.

机构信息

Department of Neurosurgery, Xinqiao Hospital, The Army Medical University, Chongqing, China.

College of Life Sciences, Chongqing Normal University, Chongqing, China.

出版信息

J Endocrinol Invest. 2021 Sep;44(9):1947-1959. doi: 10.1007/s40618-021-01510-x. Epub 2021 Feb 9.

Abstract

PURPOSE

Growth hormone-secreting pituitary adenomas (GH-PAs) are common subtypes of functional PAs. Invasive GH-PAs play a key role in restricting poor outcomes. The transcriptional changes in GH-PAs were evaluated.

METHODS

In this study, the transcriptome analysis of six different GH-PA samples was performed. The functional roles, co-regulatory network, and chromosome location of differentially expressed (DE) genes in invasive GH-PAs were explored.

RESULTS

Bioinformatic analysis revealed 101 DE mRNAs and 70 DE long non-coding RNAs (lncRNAs) between invasive and non-invasive GH-PAs. Functional enrichment analysis showed that epithelial cell differentiation and development pathways were suppressed in invasive GH-PAs, whereas the pathways of olfactory transduction, retinol metabolism, drug metabolism-cytochrome P450, and metabolism of xenobiotics by cytochrome P450 had an active trend. In the protein-protein interaction network, 11 main communities were characterized by cell- adhesion, -motility, and -cycle; transport process; phosphorus and hormone metabolic processes. The SGK1 gene was suggested to play a role in the invasiveness of GH-PAs. Furthermore, the up-regulated genes OR51B6, OR52E4, OR52E8, OR52E6, OR52N2, MAGEA6, MAGEC1, ST8SIA6-AS1, and the down-regulated genes GAD1-AS1 and SPINT1-AS1 were identified in the competing endogenous RNA network. The RT-qPCR results further supported the aberrant expression of those genes. Finally, the enrichment of DE genes in chromosome 11p15 and 12p13 regions were detected.

CONCLUSION

Our findings provide a new perspective for studies evaluating the underlying mechanism of invasive GH-PAs.

摘要

目的

生长激素分泌性垂体腺瘤(GH-PAs)是功能性 PA 的常见亚型。侵袭性 GH-PAs 在限制不良结局方面起着关键作用。评估了 GH-PAs 的转录变化。

方法

本研究对六种不同 GH-PA 样本进行了转录组分析。探讨了侵袭性 GH-PAs 中差异表达(DE)基因的功能作用、共调控网络和染色体位置。

结果

生物信息学分析显示,侵袭性和非侵袭性 GH-PAs 之间有 101 个 DE mRNAs 和 70 个 DE 长非编码 RNA(lncRNA)。功能富集分析表明,侵袭性 GH-PAs 中上皮细胞分化和发育途径受到抑制,而嗅觉转导、视黄醇代谢、药物代谢-细胞色素 P450 和细胞色素 P450 代谢外来化合物的途径呈活跃趋势。在蛋白质-蛋白质相互作用网络中,有 11 个主要社区的特征是细胞粘附、运动和周期;运输过程;磷和激素代谢过程。SGK1 基因被认为在 GH-PAs 的侵袭性中发挥作用。此外,在竞争性内源性 RNA 网络中鉴定出上调基因 OR51B6、OR52E4、OR52E8、OR52E6、OR52N2、MAGEA6、MAGEC1、ST8SIA6-AS1 和下调基因 GAD1-AS1 和 SPINT1-AS1。RT-qPCR 结果进一步证实了这些基因的异常表达。最后,检测到 DE 基因在 11p15 和 12p13 区域的富集。

结论

我们的研究结果为评估侵袭性 GH-PAs 的潜在机制提供了新的视角。

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