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miR-375在调控PDPK1以促进小肠神经内分泌肿瘤进展中的机制作用:一项计算机分析

Mechanistic role of miR-375 in regulating PDPK1 to promote progression of small bowel neuroendocrine tumors: a silico analysis.

作者信息

Ren Tao, Zhou Lu, Li Zhenlong, Pan Mingmei, Han Xueqiong

机构信息

Department of Oncology, The Fifth Affiliated Hospital of Guangxi Medical University, Nanning, 530022, Guangxi, China.

Department of Oncology, The First Affiliated Hospital Of Guangxi University Of Chinese Medicine, Nanning, 530023, Guangxi, China.

出版信息

Discov Oncol. 2025 Jun 23;16(1):1187. doi: 10.1007/s12672-025-02872-x.

DOI:10.1007/s12672-025-02872-x
PMID:40549235
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12185849/
Abstract

BACKGROUND

The incidence of small bowel neuroendocrine tumors (SBNETs) is steadily increasing, new therapies are urgently needed to prolong the overall survival of patients.

OBJECTIVE

This study aimed to identify diagnostic and therapeutic candidate markers for SBNETs.

METHODS

Expression profiles of miRNAs were collected from GSE70534, and GSE103317, that of mRNAs were collected from GSE65286. Differentially expressed genes (DEmiRs, DEmRs) were analyzed between SBNETs and controls. Enrichment and coexpression analyses were carried out for DEmRs. XGBoost algorithm was used to screening feature miRNAs. Module genes in SBNETs-related pathways were selected to construct regulated network for feature miRNAs. Drug targeting prediction and immune environment evaluation were identified.

RESULTS

A total of 57 common DEmiRs with the same direction of expression were identified. Hsa - miR - 375, hsa - miR - 107, hsa - miR - 1180, hsa - miR - 330 - 3p, and hsa - miR - 328 were identified as feature miRNAs. Among the target genes of feature miRNAs, PDPK1 was the correlation between PDPK1 and the target of Lutetium-177 (177Lu)-DOTATATE was the largest, which were regulated by miR - 375. Additionally, PDPK1 showed correlations with eosinophils, cytotoxic cells, and checkpoints in SBNETs.

CONCLUSIONS

Five feature miRNAs may have a good diagnostic role for the SBNETs. MiR - 375 regulated PDPK1 may serve as an effective therapeutic candidate marker for SBNETs.

摘要

背景

小肠神经内分泌肿瘤(SBNETs)的发病率正在稳步上升,迫切需要新的治疗方法来延长患者的总生存期。

目的

本研究旨在鉴定SBNETs的诊断和治疗候选标志物。

方法

从GSE70534和GSE103317收集miRNA的表达谱,从GSE65286收集mRNA的表达谱。分析SBNETs与对照之间的差异表达基因(DEmiRs、DEmRs)。对DEmRs进行富集和共表达分析。使用XGBoost算法筛选特征miRNA。选择SBNETs相关通路中的模块基因构建特征miRNA的调控网络。进行药物靶向预测和免疫环境评估。

结果

共鉴定出57个表达方向相同的常见DEmiRs。hsa-miR-375、hsa-miR-107、hsa-miR-1180、hsa-miR-330-3p和hsa-miR-328被鉴定为特征miRNA。在特征miRNA的靶基因中,PDPK1与镥-177(177Lu)-DOTATATE的靶点相关性最大,受miR-375调控。此外,PDPK1在SBNETs中与嗜酸性粒细胞、细胞毒性细胞和检查点相关。

结论

五个特征miRNA可能对SBNETs具有良好的诊断作用。miR-375调控的PDPK1可能作为SBNETs有效的治疗候选标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9aad/12185849/5e204fdc172b/12672_2025_2872_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9aad/12185849/8b518e3d2698/12672_2025_2872_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9aad/12185849/fe10ab6060d9/12672_2025_2872_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9aad/12185849/74337a4a8190/12672_2025_2872_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9aad/12185849/deafcaeb8db2/12672_2025_2872_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9aad/12185849/b2d343a6449b/12672_2025_2872_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9aad/12185849/5e204fdc172b/12672_2025_2872_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9aad/12185849/8b518e3d2698/12672_2025_2872_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9aad/12185849/93a1b24eb5c7/12672_2025_2872_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9aad/12185849/fe10ab6060d9/12672_2025_2872_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9aad/12185849/74337a4a8190/12672_2025_2872_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9aad/12185849/deafcaeb8db2/12672_2025_2872_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9aad/12185849/b2d343a6449b/12672_2025_2872_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9aad/12185849/5e204fdc172b/12672_2025_2872_Fig7_HTML.jpg

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