Long non-coding RNA HOXC-AS3 promotes proliferation and metastasis of esophageal squamous carcinoma - Research Open Access

Sep 23, 2026

Uploaded by Margaret

Esophageal squamous cell carcinoma (ESCC) shows high morbidity and mortality, and the molecular roles of long non-coding RNAs remain a key research need. HOXC-AS3 expression is elevated in ESCC tissues, and it modulates ESCC cell proliferation and migration. HOXC-AS3 knockdown increases apoptosis and induces cell-cycle arrest. RNA sequencing and Gene Ontology indicate downstream genes enriched in proliferation and migration pathways, while RIP and CHIP support HOXC-AS3 recruitment to the WNT3A promoter via YBX1, supporting HOXC-AS3 as a novel oncogenic driver.

LanguageEnglish

CategoryHealthcare

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Abstract

Introduction

Methods and materials

Hu etal. BMC Cancer (2026) 26:381 [https://doi.org/10.1186/s12885-026-15672-5](https://doi.org/10.1186/s12885-026-15672-5) BMC Cancer RESEARCH Open Access Long non-coding RNA HOXC-AS3 promotes proliferation and metastasis of esophageal squamous carcinoma by targeting WNT3A through binding toYBX1 Shuo Hu1†, Qi Wang2†, HaiXing Wei3†, HaiJun Sun1, ZhiHua Li2, ZhiCheng He2, XiangLong Pan2 and WeiBing Wu2* Abstract Esophageal squamous cell carcinoma (ESCC) is one of the malignancies with high morbidity and mortality rates. Previous studies have demonstrated the critical roles of long non-coding RNAs (lncRNAs) in cell differentiation, embryonic development and cancer progression. The lncRNA HOXC-AS3 has been shown to exert pro-carcinogenic effects in adenocarcinoma, gastric cancer and breast cancer; however, its biological function in ESCC remains unclear. In the present study, HOXC-AS3 expression was found to be elevated in ESCC tissues. We discovered that HOXC-AS3 regulates the proliferation and migration of ESCC cells. Flow cytometry assays indicated that knockdown of HOXC-AS3 led to increased apoptosis and cell cycle arrest in ESCC cells. RNA sequencing and Gene Ontology findings revealed that the downstream genes regulated by HOXC-AS3 were primarily enriched in signaling pathways associated with cell proliferation and migration. RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (CHIP) experiments confirmed that HOXC-AS3 can be recruited to the promoter region of the WNT3A gene by binding to YBX1 . These findings provide evidence of lncRNA HOXC-AS3 functions as a novel oncogene in ESCC. Keywords ESCC, LncRNA HOXC-AS3, YBX1, WNT3A †Shuo Hu, Qi Wang and HaiXing Wei contributed equally to this work and they should be identified as co-first authors. *Correspondence: WeiBing Wu [wuweibing95@163.com](wuweibing95@163.com) 1Department of Thoracic Surgery, The First People’s Hospital of Lianyungang, Lianyungang, Jiangsu Province, China 2Department of Thoracic Surgery, The First Affiliated Hospital of Nanjing Medical University, No. 300, Guangzhou Road, Nanjing, Jiangsu Province 210029, China 3Department of Thoracic Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China Introduction Esophageal squamous cell carcinoma (ESCC), the most common histological type of esophageal cancer, is particularly prevalent in East Asia and the Middle East, with high morbidity and mortality rates [1]. China is among the regions with high incidence [2]. In recent years, advances have been made in chemotherapy and radiotherapy, and significant breakthroughs have also occurred in molecular targeted therapy and immunotherapy. However, the 5-year overall survival rate for patients with recurrent ESCC remains below 20%[3, 4]. Therefore, understanding the molecular mechanisms underlying ESCC development and identifying effective © The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creati](http://creati)[vecommons.org/licenses/by-nc-nd/4.0/

FAQs

What role does lncRNA HOXC-AS3 play in esophageal squamous cell carcinoma (ESCC)?

HOXC-AS3 is elevated in ESCC tissues and promotes ESCC cell proliferation and migration, supporting its oncogenic function.

How does HOXC-AS3 affect ESCC cell apoptosis and the cell cycle?

HOXC-AS3 knockdown increases apoptosis and causes cell-cycle arrest in ESCC cells.

How is HOXC-AS3 linked to WNT3A and YBX1 mechanistically?

HOXC-AS3 binds to YBX1 and helps recruit YBX1 to the WNT3A promoter region, leading to regulation of WNT3A expression and downstream pro-tumor signaling.

Sep 23, 2026

Uploaded by Margaret