下调乳铁传递蛋白可增强鼻咽癌的放射敏感性。

Down regulation of lactotransferrin enhanced radio-sensitivity of nasopharyngeal carcinoma.

机构信息

Department of Pathogenic Biology, School of Basic Medicine, Qingdao University, 308 Ningxia Road, Qingdao, 266021, China; Qingdao Shinan District Center for Disease Control and Prevention, 90 Xuzhou Road, Qingdao, 266021, China.

Department of Pathogenic Biology, School of Basic Medicine, Qingdao University, 308 Ningxia Road, Qingdao, 266021, China.

出版信息

Comput Biol Chem. 2021 Feb;90:107426. doi: 10.1016/j.compbiolchem.2020.107426. Epub 2020 Dec 8.

DOI:10.1016/j.compbiolchem.2020.107426

PMID:33352501

Abstract

INTRODUCTION

It is reported that LTF had a radiation resistance effect, and its expression in nasopharyngeal carcinoma (NPC) was significantly down-regulated. However, the mechanism of down-regulated LTF affecting the sensitivity of radiotherapy has remained elusive.

METHODS

We re-analyzed the microarray data GSE36972 and GSE48503 to find differentially expressed genes (DEGs) in NPC cell line 5-8 F transfected with LTF or vector control, and the DEGs between radio-resistant and radio-sensitive NPC cell lines. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment and protein-protein interaction network (PPI) analysis of DEGs were performed to obtain the node genes. The target genes of miR-214 were also predicted to complement the mechanism associated with radiotherapy resistance because it could directly target LTF.

RESULTS

This study identified 1190 and 1279 DEGs, respectively. GO and KEGG analysis showed that apoptotic process and proliferation, PI3K-Akt signaling pathway were significantly enriched pathways. Four nodes (DUSP1, PPARGC1A, FOS and SMARCA1) associated with LTF were screened. And 42 target genes of miR-214 were cross-linked to radiotherapy sensitivity.

CONCLUSIONS

The present study demonstrates the possible molecular mechanism that the down-regulated LTF enhances the radiosensitivity of NPC cells through interaction with DUSP1, PPARGC1A, FOS and SMARCA1, and miR-214 as its superior negative regulator may play a role in regulating the radiotherapy effect.

摘要

简介

据报道，LTF 具有辐射抗性作用，其在鼻咽癌（NPC）中的表达显著下调。然而，下调的 LTF 影响放射治疗敏感性的机制仍不清楚。

方法

我们重新分析了微阵列数据 GSE36972 和 GSE48503，以找到转染 LTF 或空载体对照的 NPC 细胞系 5-8F 中的差异表达基因（DEGs），以及放射抵抗和放射敏感 NPC 细胞系之间的 DEGs。对 DEGs 进行基因本体论（GO）、京都基因与基因组百科全书（KEGG）富集和蛋白质-蛋白质相互作用网络（PPI）分析，以获得节点基因。还预测了 miR-214 的靶基因，以补充与放射治疗抵抗相关的机制，因为它可以直接靶向 LTF。

结果

本研究分别鉴定出 1190 和 1279 个 DEGs。GO 和 KEGG 分析表明，凋亡过程和增殖、PI3K-Akt 信号通路是显著富集的途径。筛选出与 LTF 相关的四个节点（DUSP1、PPARGC1A、FOS 和 SMARCA1）。并且，miR-214 的 42 个靶基因与放射治疗敏感性相关。