LINC00330/CCL2 axis-mediated ESCC TAM reprogramming affects tumor progression

Area of Science:

• Oncology
• Molecular Biology
• Immunology

Background:

• Tumor-associated macrophages (TAMs) are critical in esophageal squamous cell carcinoma (ESCC) progression, metastasis, and recurrence.
• While aberrant long noncoding RNA (lncRNA) expression is known in ESCC, their role in TAM reprogramming remains unclear.

Purpose of the Study:

• To investigate the role of lncRNAs in TAM reprogramming during ESCC progression.
• To identify specific lncRNAs involved in TAM regulation and their impact on ESCC.
• To elucidate the molecular mechanisms underlying LINC00330's function in ESCC and TAMs.

Main Methods:

• Identified ESCC TAM-related lncRNAs by intersecting differentially expressed and immune-related lncRNAs.
• Analyzed LINC00330 expression and clinical relevance using TCGA and patient samples.
• Investigated LINC00330's effect on ESCC progression and TAM reprogramming through in vitro and in vivo experiments, including co-culture and transcriptomic analysis.

Main Results:

• LINC00330 was significantly downregulated in ESCC and associated with poor outcomes.
• LINC00330 overexpression inhibited ESCC proliferation, invasion, EMT, and tumorigenicity.
• LINC00330 promoted TAM reprogramming, which subsequently inhibited ESCC progression by binding to CCL2 and affecting downstream signaling.

Conclusions:

• LINC00330 inhibits ESCC progression by disrupting the CCL2/CCR2 axis in both autocrine and paracrine manners.
• LINC00330 impedes CCL2-mediated TAM reprogramming, offering a novel mechanism.
• The LINC00330/CCL2 axis presents potential targets for novel immunotherapies in ESCC.