The LGALS9/miR-491-5p Axis Regulates CD8+ T Cell Function and Inhibits the Progression of Gastric Cancer

Sep 29, 2026

Uploaded by Noah

Gastric cancer is a prevalent gastrointestinal malignancy marked by limited treatment efficacy and frequent recurrence. This study shows LGALS9 is highly expressed in gastric cancer and promotes progression by shaping CD8+ T cell infiltration. LGALS9 genetic knockout reverses T cell function, reduces immunosuppression, and increases cytotoxic activity against gastric cancer cells. miR-491-5p is identified as a tumor-suppressive microRNA that targets LGALS9 to regulate T cell–mediated immunity, supporting the LGALS9–miR-491-5p axis as a potential therapeutic target.

LanguageEnglish

CategoryHealthcare

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Pages13

Reading Time33 min

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Abstract

Introduction

Background and related mechanisms

MicroRNAs and target regulation

Cancer Science ORIGINAL ARTICLE OPEN ACCESS The LGALS9/miR-491-5p Axis Regulates CD8 + T Cell Function and Inhibits the Progression of Gastric Cancer Wanzhong Huang1,2 | Wei Zheng1,2 | Dagao Zhu1,2 | Zhi Sun3,4 | Wei Lu3,4 | Jun Tao3,4 | Chen Liu5,6 | Liangliang Li1,2 | Yingli Zhou1,2 | Honghong Fan1,2 | Hong Tao1,2 | Wenjuan Li7,8 1Department of Medical Oncology, Tonglin People's Hospital, Tonglin, Anhui, China | 2Department of Medical Oncology, Tongling Hospital Affiliated to Bengbu Medical University, Tonglin, Anhui, China | 3Department of Gastrointestinal Surgery, Tonglin People's Hospital, Tonglin, Anhui, China | 4Department of Gastrointestinal Surgery, Tongling Hospital Affiliated to Bengbu Medical University, Tonglin, Anhui, China | 5Department of Pathology, Tonglin People's Hospital, Tonglin, Anhui, China | 6Department of Pathology, Tongling Hospital Affiliated to Bengbu Medical University, Tonglin, Anhui, China | 7Department of Medical Oncology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China | 8Department of Medical Oncology, Anhui Provincial Cancer Hospital, Hefei, Anhui, China Correspondence: Wenjuan Li ([lwj1015@126.com](lwj1015@126.com)) Received: 4 April 2025 | Revised: 11 October 2025 | Accepted: 14 October 2025 Funding: This work was supported by the Natural Science Projects of Bengbu Medical College (2023BYZD013) . Keywords: gastric cancer | immunosuppression | LGALS9 | miR-491-5p | T cell ABSTRACT Gastric cancer is a prevalent and clinically significant gastrointestinal malignancy worldwide. Gastric cancer is characterized by limited treatment efficacy and a high recurrence rate. In this study, we found that LGALS9 was highly expressed in gastric cancer and may contribute to disease progression by modulating the infiltration of CD8+ T cells. Genetic knockout of LGALS9 reversed T cell function, attenuated immunosuppression, and enhanced the cytotoxic activity ofT cells to kill gastric cancer cells. Furthermore, miR-491-5p was identified as a potential suppressor in gastric cancer. The microRNA miR-491-5p regulated T cellmediated immunity by targeting and inhibiting LGALS9, which was similar to the effect of LGALS9 knockout. Overall, the key target LGALS9 and its inhibitor miR-491-5p represent promising potential for treating gastric cancer. 1 | Introduction Gastric cancer is a prevalent and clinically significant gastrointestinal malignancy worldwide. Gastric cancer is characterized by limited treatment efficacy and a high recurrence rate. The effective management of this disease requires a comprehensive understanding of its potential pathogenic mechanisms. Galectin-9, encoded by LGALS9, has emerged as a promising therapeutic target in the treatment of gastric cancer and has attracted considerable attention. LGALS9 plays an important role in multiple tumor processes, such as tumor cell adhesion, metastasis, immune escape, and tumor angiogenesis. Melanoma cells expressing LGALS9 are capable of forming colonies, whereas those lacking LGALS9 expression fail to do so [1] . Similarly, MCF7 breast cancer cells with high LGALS9 expression form clusters, which is a phenomenon not observed in cells with low LGALS9 expression [2] . The upregulation of LGALS9 also regulates E-selectin levels in LoVo colon carcinoma cells [3] . Additionally, the immunosuppressive effect of LGALS9 is considered a mechanism through which Epstein–Barr virus-infected nasopharyngeal carcinoma cells evade immune surveillance [4] . A recent | Abbreviations: CCK-8, cell counting kit-8; CHOL, cholangiocarcinoma; DO, disease ontology; EdU, 5-ethynyl-2′-deoxyuridine; EGFR, epidermal growth factor receptor; EMT, epithelial-mesenchymal transition; HCC, hepatocellular carcinoma; HER2, human epidermal growth factor receptor 2; IHC, immunohistochemistry; KEGG, Kyoto Encyclopedia of Genes and Genomes; KO, knockout; MFC, mous

FAQs

What role does LGALS9 play in gastric cancer progression?

LGALS9 is highly expressed in gastric cancer and may promote disease progression by modulating CD8+ T cell infiltration and contributing to immunosuppression.

How does LGALS9 knockout affect CD8+ T cell function?

Genetic knockout of LGALS9 reverses T cell function, attenuates immunosuppression, and enhances the cytotoxic activity of T cells against gastric cancer cells.

How does miR-491-5p relate to LGALS9 and T cell–mediated immunity?

miR-491-5p targets and inhibits LGALS9, regulating T cell–mediated immunity similarly to LGALS9 knockout and supporting an overall therapeutic potential for the LGALS9–miR-491-5p axis.

Sep 29, 2026

Uploaded by Noah