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HOXA11反义RNA通过调控胰腺癌中IFNL和HMGB家族基因促进淋巴结转移。

HOXA11-As Promotes Lymph Node Metastasis Through Regulation of IFNL and HMGB Family Genes in Pancreatic Cancer.

作者信息

Nishiyama Hayato, Niinuma Takeshi, Kitajima Hiroshi, Ishiguro Kazuya, Yamamoto Eiichiro, Sudo Gota, Sasaki Hajime, Yorozu Akira, Aoki Hironori, Toyota Mutsumi, Kai Masahiro, Suzuki Hiromu

机构信息

Department of Molecular Biology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.

Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan.

出版信息

Int J Mol Sci. 2024 Nov 30;25(23):12920. doi: 10.3390/ijms252312920.

DOI:10.3390/ijms252312920
PMID:39684631
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11641524/
Abstract

Recent studies have shown that long noncoding RNAs (lncRNAs) play pivotal roles in the development and progression of cancer. In the present study, we aimed to identify lncRNAs associated with lymph node metastasis in pancreatic ductal adenocarcinoma (PDAC). We analyzed data from The Cancer Genome Atlas (TCGA) database to screen for genes overexpressed in primary PDAC tumors with lymph node metastasis. Our screen revealed 740 genes potentially associated with lymph node metastasis, among which were multiple lncRNA genes located in the HOXA locus, including HOXA11-AS. Elevated expression of HOXA11-AS was associated with more advanced tumor stages and shorter overall survival in PDAC patients. HOXA11-AS knockdown suppressed proliferation and migration of PDAC cells. RNA-sequencing analysis revealed that HOXA11-AS knockdown upregulated interferon lambda (IFNL) family genes and downregulated high-mobility group box (HMGB) family genes in PDAC cells. Moreover, HMGB3 knockdown suppressed proliferation and migration by PDAC cells. These results suggest that HOXA11-AS contributes to PDAC progression, at least in part, through regulation of IFNL and HMGB family genes and that HOXA11 AS is a potential therapeutic target in PDAC.

摘要

最近的研究表明，长链非编码RNA（lncRNA）在癌症的发生和发展过程中起着关键作用。在本研究中，我们旨在鉴定与胰腺导管腺癌（PDAC）淋巴结转移相关的lncRNA。我们分析了癌症基因组图谱（TCGA）数据库中的数据，以筛选在伴有淋巴结转移的原发性PDAC肿瘤中过表达的基因。我们的筛选揭示了740个可能与淋巴结转移相关的基因，其中包括位于HOXA基因座的多个lncRNA基因，包括HOXA11-AS。HOXA11-AS的表达升高与PDAC患者更晚期的肿瘤分期和更短的总生存期相关。HOXA11-AS敲低抑制了PDAC细胞的增殖和迁移。RNA测序分析表明，HOXA11-AS敲低上调了PDAC细胞中的干扰素λ（IFNL）家族基因，并下调了高迁移率族蛋白（HMGB）家族基因。此外，HMGB3敲低抑制了PDAC细胞的增殖和迁移。这些结果表明，HOXA11-AS至少部分地通过调节IFNL和HMGB家族基因促进PDAC进展，并且HOXA11-AS是PDAC中的一个潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66c2/11641524/2e58c5664507/ijms-25-12920-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66c2/11641524/1df18478a508/ijms-25-12920-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66c2/11641524/2e58c5664507/ijms-25-12920-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66c2/11641524/1df18478a508/ijms-25-12920-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66c2/11641524/9767b1fdda82/ijms-25-12920-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66c2/11641524/ed3fe7beaf79/ijms-25-12920-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66c2/11641524/1d5adccd2a17/ijms-25-12920-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66c2/11641524/2e58c5664507/ijms-25-12920-g005.jpg

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本文引用的文献

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Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.2022 年全球癌症统计数据：全球 185 个国家和地区 36 种癌症的发病率和死亡率全球估计数。
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