Work

LIG1 overexpression enhances DNA repair and immune escape leading to poor prognosis in osteosarcoma

Year: 2025

Type: article

Abstract: BACKGROUND: Osteosarcoma (OS), the most common primary malignant bone tumor in adolescents, exhibits high metastasis and poor response to current therapies. DNA Ligase I (LIG1), a key enzyme in DNA replication and repair, has been implicated in multiple cancers, but its role in OS remains unclear. METHODS: Transcriptomic and clinical data from the TCGA-OS cohort were analyzed to assess LIG1 expression, immune infiltration, and prognosis. Functional studies using gain- and loss-of-function assays evaluated its impact on OS cell viability, clonogenicity, and apoptosis. The effects of LIG1 inhibition by epigallocatechin gallate (EGCG) were also examined. RESULTS: LIG1 was significantly upregulated in OS tissues and correlated with reduced overall and disease-free survival. High LIG1 expression was linked to an immunosuppressive microenvironment with fewer cytotoxic T cells and increased Tregs and M2 macrophages. Functionally, LIG1 promoted OS cell proliferation and survival, while its inhibition by EGCG suppressed tumor growth. CONCLUSIONS: LIG1 drives OS progression and immune evasion by remodeling the tumor microenvironment. It serves as an independent prognostic biomarker and a potential therapeutic target, particularly in combination with immune checkpoint blockade.

Source: European journal of medical research

DOI: 10.1186/s40001-025-03647-4

Authors: Wenju Fu, Guangman Tang, Yu Tang, Peng Yan, Qiangqiang Wang

Institutions: Taizhou Second People's Hospital, Yangzhou University, Chinese People's Liberation Army, Binzhou Medical University, Huazhong University of Science and Technology

Language: English

Topic: Sarcoma Diagnosis and Treatment

Subfield: Pulmonary and Respiratory Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,190