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转录组学揭示了 NTRK1 对人神经细胞系内质网应激反应相关基因的影响。

Transcriptomics reveals the effects of NTRK1 on endoplasmic reticulum stress response-associated genes in human neuronal cell lines.

机构信息

Department of Anesthesiology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.

Department of Anesthesiology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei Province, China.

出版信息

PeerJ. 2023 Apr 12;11:e15219. doi: 10.7717/peerj.15219. eCollection 2023.

Abstract

BACKGROUND

gene, encoding TrkA, is essential for the nervous system and drives a variety of biological processes, including pain. Given the unsatisfied analgesic effects of some new drugs targeting in clinic, a deeper understanding for the mechanism of in neurons is crucial.

METHODS

We assessed the transcriptional responses in SH-SY5Y cells with overexpression using bioinformatics analysis. GO and KEGG analyses were performed, PPI networks were constructed, and the functional modules and top 10 genes were screened. Subsequently, hub genes were validated using RT-qPCR.

RESULTS

A total of 419 DEGs were identified, including 193 upregulated and 226 downregulated genes. GO showed that upregulated genes were mainly enriched in response to endoplasmic reticulum (ER) stress, protein folding in ER, ., and downregulated genes were highly enriched in a series of cellular parts and cellular processes. KEGG showed DEGs were enriched in protein processing in ER and pathways associated with cell proliferation and migration. The finest module was dramatically enriched in the ER stress response-related biological process. The verified seven hub genes consisted of five upregulated genes (COL1A1, P4HB, HSPA5, THBS1, and XBP1) and two downregulated genes (CCND1 and COL3A1), and almost all were correlated with response to ER stress.

CONCLUSION

Our data demonstrated that significantly influenced the gene transcription of ER stress response in SH-SY5Y cells. It indicated that ER stress response could contribute to various functions of -dependent neurons, and therefore, ER stress response-associated genes need further study for neurological dysfunction implicated in .

摘要

背景

编码 TrkA 的基因对于神经系统是必需的,它驱动着包括疼痛在内的多种生物学过程。鉴于一些针对 的新药在临床上的镇痛效果不尽如人意,深入了解 在神经元中的作用机制至关重要。

方法

我们使用生物信息学分析评估了过表达 的 SH-SY5Y 细胞中的转录反应。进行了 GO 和 KEGG 分析,构建了 PPI 网络,并筛选了功能模块和前 10 个基因。随后,使用 RT-qPCR 验证了枢纽基因。

结果

共鉴定出 419 个差异表达基因,包括 193 个上调基因和 226 个下调基因。GO 显示上调基因主要富集在对内质网(ER)应激、内质网中蛋白质折叠、、的反应中,而下调基因则高度富集在一系列细胞部分和细胞过程中。KEGG 显示差异表达基因富集在 ER 蛋白加工和与细胞增殖和迁移相关的途径中。最佳模块显著富集在 ER 应激反应相关的生物学过程中。验证的七个枢纽基因包括五个上调基因(COL1A1、P4HB、HSPA5、THBS1 和 XBP1)和两个下调基因(CCND1 和 COL3A1),几乎所有基因都与 ER 应激反应相关。

结论

我们的数据表明, 显著影响了 SH-SY5Y 细胞中 ER 应激反应的基因转录。这表明 ER 应激反应可能有助于 依赖性神经元的各种功能,因此,需要进一步研究与 ER 应激反应相关的基因,以了解其在神经功能障碍中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4933/10105561/517d6874dac1/peerj-11-15219-g001.jpg

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