HOXA11-AS Promotes Lymph Node Metastasis Through Regulation of IFNL and HMGB Family Genes in Pancreatic Cancer - Research Article

Sep 22, 2026

Recent studies indicate long noncoding RNAs (lncRNAs) are central to cancer development and progression. This study identifies lncRNAs linked to lymph node metastasis in pancreatic ductal adenocarcinoma (PDAC) by mining TCGA data for genes overexpressed in tumors with nodal spread. HOXA11-AS shows stronger association with advanced stage and shorter overall survival. Silencing HOXA11-AS inhibits PDAC proliferation and migration, and alters interferon lambda (IFNL) and HMGB family gene expression, implicating HOXA11-AS as a therapeutic target.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages12

Reading Time30 min

AccessFree to download

Introduction

Clinical significance of lymph node metastasis in PDAC

Genetic drivers of PDAC progression

Role of lncRNAs in cancer biology

Article HOXA11-As Promotes Lymph Node Metastasis Through Regulation of IFNL and HMGB Family Genes in Pancreatic Cancer Hayato Nishiyama 1,†, Takeshi Niinuma 1,†, Hiroshi Kitajima 1, Kazuya Ishiguro 1, Eiichiro Yamamoto 1, Gota Sudo 2, Hajime Sasaki 2, Akira Yorozu 1,3, Hironori Aoki 1, Mutsumi Toyota 1, Masahiro Kai 1 and Hiromu Suzuki 1, * Citation: Nishiyama, H.; Niinuma, T.; Kitajima, H.; Ishiguro, K.; Yamamoto, E.; Sudo, G.; Sasaki, H.; Yorozu, A.; Aoki, H.; Toyota, M.; et al. HOXA11-As Promotes Lymph Node Metastasis Through Regulation of IFNL and HMGB Family Genes in Pancreatic Cancer. Int. J. Mol. Sci. 2024, 25, 12920. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/ijms252312920](10.3390/ijms252312920) Academic Editor: Pinar UysalOnganer Received: 17 November 2024 Revised: 26 November 2024 Accepted: 28 November 2024 Published: 30 November 2024 Copyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 Department of Molecular Biology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan; [a19m073@sapmed.ac.jp](a19m073@sapmed.ac.jp) (H.N.); [niinuma@sapmed.ac.jp](niinuma@sapmed.ac.jp) (T.N.); [kitaji@sapmed.ac.jp](kitaji@sapmed.ac.jp) (H.K.); [k05m010@yahoo.co.jp](k05m010@yahoo.co.jp) (K.I.); [eiichiro@xa3.so-net.ne.jp](eiichiro@xa3.so-net.ne.jp) (E.Y.); [yorozuakira0110@gmail.com](yorozuakira0110@gmail.com) (A.Y.); [hironori_a1123@yahoo.co.jp](hironori_a1123@yahoo.co.jp) (H.A.); [mutoyota@sapmed.ac.jp](mutoyota@sapmed.ac.jp) (M.T.); [kai@sapmed.ac.jp](kai@sapmed.ac.jp) (M.K.) 2 Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan; [gotasudo@gmail.com](gotasudo@gmail.com) (G.S.); [kiti4989@yahoo.co.jp](kiti4989@yahoo.co.jp) (H.S.) 3 Department of Otolaryngology-Head and Neck Surgery, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan * [Correspondence: hsuzuki@sapmed.ac.jp](Correspondence: hsuzuki@sapmed.ac.jp) † These authors contributed equally to this work. 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. Keywords: PDAC; lncRNA; lymph node metastasis; IFN-λ; HMGB3 1. Introduction Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal forms of cancer and was ranked as the sixth most common cause of cancer mortality in 2022 [1] . Approximately 80–85% of PDAC patients present with advanced, unresectable disease, which contributes to its lethality [2] . In recent yea

FAQs

What role does HOXA11-AS play in pancreatic cancer progression?

HOXA11-AS is associated with more advanced PDAC stages and shorter overall survival. Knockdown of HOXA11-AS suppresses PDAC cell proliferation and migration.

How was HOXA11-AS linked to lymph node metastasis?

The study screened for genes overexpressed in primary PDAC tumors with lymph node metastasis using TCGA data, identifying multiple lncRNAs within the HOXA locus, including HOXA11-AS.

Which gene families are regulated after HOXA11-AS knockdown?

RNA-sequencing showed HOXA11-AS knockdown upregulates interferon lambda (IFNL) family genes and downregulates HMGB family genes in PDAC cells.

Sep 22, 2026

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