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HOXA13 通过上调 Snail 和 MMP-2 的表达促进鼻咽癌细胞 HNE1 的增殖、迁移和侵袭。

HOXA13 promotes the proliferation, migration, and invasion of nasopharyngeal carcinoma HNE1 cells by upregulating the expression of Snail and MMP-2.

机构信息

Department of Otolaryngology Head and Neck Surgery, The Affiliated Hospital of Southwest Medical University, NO: 25, Taiping Street, Jiangyang District, Luzhou, 646000, China.

Department of Otolaryngology Head and Neck Surgery, The First People's Hospital of Yibin, Yibin, 644000, China.

出版信息

Sci Rep. 2023 Aug 10;13(1):12978. doi: 10.1038/s41598-023-40041-8.

Abstract

Homeobox A13 (HOXA13) has been verified as an oncogen in some malignancies. However, its role in nasopharyngeal carcinoma (NPC) is still unclear. This study aims to explore the role of HOXA13 in NPC and its underlying mechanism. The mRNA expression of HOXA13 in NPC was obtained from the GSE53819 and GSE64634 datasets in the Gene Expression Omnibus (GEO) database. MTT, colony formation and transwell assays and xenograft tumour models were used to investigate the effects of HOXA13 on NPC HNE1 cells in vitro and in vivo. The expression of HOXA13, epithelial-mesenchymal transition-transcription factor (EMT-TF) Snail and matrix metalloproteinase 2 (MMP-2) was detected by immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. The results showed that HOXA13 was upregulated in NPC. Silencing HOXA13 suppressed the proliferation, migration, and invasion of HNE1 cells, which inhibited tumour growth, while overexpression of HOXA13 induced the opposite effects. In addition, the expression of Snail and MMP-2 at the transcriptional and protein levels was associated with the expression of HOXA13. In summary, our results suggest that HOXA13 plays a role as a cancer-promoting gene in NPC. The underlying mechanism may be related to the upregulation of Snail and MMP-2.

摘要

Homeobox A13 (HOXA13) 已被证实为某些恶性肿瘤的致癌基因。然而,其在鼻咽癌(NPC)中的作用尚不清楚。本研究旨在探讨 HOXA13 在 NPC 中的作用及其潜在机制。从基因表达综合数据库(GEO)中的 GSE53819 和 GSE64634 数据集获得 NPC 中 HOXA13 的 mRNA 表达。MTT、集落形成和 Transwell 分析以及异种移植肿瘤模型用于研究 HOXA13 对 NPC HNE1 细胞的体外和体内作用。通过免疫组织化学、实时定量聚合酶链反应(qRT-PCR)和 Western blot 检测 HOXA13、上皮-间充质转化转录因子(EMT-TF)Snail 和基质金属蛋白酶 2(MMP-2)的表达。结果表明,HOXA13 在 NPC 中上调。沉默 HOXA13 抑制 HNE1 细胞的增殖、迁移和侵袭,从而抑制肿瘤生长,而过表达 HOXA13 则诱导相反的效果。此外,Snail 和 MMP-2 的表达在转录和蛋白水平上与 HOXA13 的表达相关。综上所述,我们的研究结果表明 HOXA13 在 NPC 中作为致癌基因发挥作用。其潜在机制可能与 Snail 和 MMP-2 的上调有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22c4/10415404/76fdced635da/41598_2023_40041_Fig1_HTML.jpg

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