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基于 RNA-Seq 分析鉴定鼻咽癌中的关键假基因。

Identification of key pseudogenes in nasopharyngeal carcinoma based on RNA-Seq analysis.

机构信息

Department of Otolaryngology, Eye, Ear, Nose and Throat Hospital, Shanghai Key Clinical Disciplines of Otorhinolaryngology, Fudan University, 83 Fen Yang Road, Shanghai, 200031, China.

Research Units of New Technologies of Endoscopic Surgery in Skull Base Tumor, Chinese Academy of Medical Sciences, Beijing, 100730, China.

出版信息

BMC Cancer. 2021 Apr 30;21(1):483. doi: 10.1186/s12885-021-08211-x.

Abstract

BACKGROUND

Nasopharyngeal carcinoma (NPC) is a malignant head and neck tumor, and more than 70% of new cases are in East and Southeast Asia. However, association between NPC and pseudogenes playing important roles in genesis of multiple tumor types is still not clear and needs to be investigated.

METHODS

Using RNA-Sequencing (RNA-seq) technology, we analyzed pseudogene expression in 13 primary NPC and 6 recurrent NPC samples as well as their paracancerous counterparts. Quantitative PCR was used to validate the differentially expressed pseudogenes.

RESULTS

We found 251 differentially expressed pseudogenes including 73 up-regulated and 178 down-regulated ones between primary NPC and paracancerous tissues. Enrichment analysis of gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were conducted to filter out the key pseudogenes. We reported that pseudogenes from cytochrome P450 (CYP) family, such as CYP2F2P, CYP2G1P, CYP4F24P, CYP2B7P and CYP2G2P were significantly down-regulated in NPC compared to paracancerous tissues, while IGHV1OR15-2, IGHV3-11, FCGR1CP and IGHV3-69-1 belonging to Fc gamma receptors were significantly up-regulated. CYP2B7P, CYP2F2P and CYP4F26P were enriched in arachidonic acid metabolism pathway. The qRT-PCR analysis validated the lower expression of pseudogenes CYP2F2P and CYP2B7P in NPC tissues and cell lines compared to paracancerous tissues and normal human nasopharyngeal epithelial cell line. CYP2B7P overexpression weakened migratory and invasive capacity of NPC cell line. Moreover, the expression pattern of those pseudogenes in recurrent NPC tissues was different from the primary NPC.

CONCLUSION

This study suggested the role of pseudogenes in tumorigenesis and progression, potentially functioning as therapeutic targets to NPC.

摘要

背景

鼻咽癌(NPC)是一种恶性头颈部肿瘤,超过 70%的新发病例发生在东亚和东南亚地区。然而,NPC 与在多种肿瘤类型的发生中起重要作用的假基因之间的关联尚不清楚,需要进一步研究。

方法

我们使用 RNA 测序(RNA-seq)技术分析了 13 例原发性 NPC 和 6 例复发性 NPC 样本及其癌旁组织中的假基因表达。采用定量 PCR 验证差异表达的假基因。

结果

我们发现 251 个差异表达的假基因,包括 73 个上调和 178 个下调的假基因,在原发性 NPC 和癌旁组织之间。对基因本体(GO)和京都基因与基因组百科全书(KEGG)通路的富集分析,筛选出关键的假基因。我们报告说,细胞色素 P450(CYP)家族的假基因,如 CYP2F2P、CYP2G1P、CYP4F24P、CYP2B7P 和 CYP2G2P,在 NPC 中与癌旁组织相比明显下调,而属于 Fc 受体的 IGHV1OR15-2、IGHV3-11、FCGR1CP 和 IGHV3-69-1 则明显上调。CYP2B7P、CYP2F2P 和 CYP4F26P 富集在花生四烯酸代谢途径中。qRT-PCR 分析验证了 NPC 组织和细胞系中假基因 CYP2F2P 和 CYP2B7P 的表达低于癌旁组织和正常鼻咽上皮细胞系。CYP2B7P 的过表达削弱了 NPC 细胞系的迁移和侵袭能力。此外,这些假基因在复发性 NPC 组织中的表达模式与原发性 NPC 不同。

结论

本研究提示假基因在肿瘤发生和进展中的作用,可能成为 NPC 的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf95/8088053/5fe09719a893/12885_2021_8211_Fig1_HTML.jpg

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