m6A-Modified BASP1 Regulates IL6 Expression to Induce TAM Infiltration to Promote Gastric Cancer Progression

Area of Science:

• Oncology
• Molecular Biology
• Immunology

Background:

• Gastric cancer (GC) is an aggressive malignancy with a poor patient prognosis.
• Understanding the molecular mechanisms driving GC progression and identifying therapeutic targets are critical.

Purpose of the Study:

• To investigate the role of N6-methyladenosine (m6A) in regulating Brain Abundant Signal Protein 1 (BASP1) expression in GC.
• To elucidate the functional impact of BASP1 on GC progression, including its effects on the tumor microenvironment (TME) via interleukin-6 (IL6) and M2 macrophages.
• To explore the involvement of the PI3K/AKT signaling pathway in BASP1-mediated GC pathogenesis.

Main Methods:

• Analysis of GC patient data from The Cancer Genome Atlas (TCGA).
• In vitro studies using GC cell lines and in vivo experiments with nude mice.
• Manipulation of BASP1 expression using lentiviral vectors.
• Assessment of cellular functions (viability, migration, invasion, apoptosis) and molecular mechanisms (m6A modification, IL6 levels, macrophage polarization, PI3K/AKT pathway activation).

Main Results:

• BASP1 expression is elevated in GC tissues and correlates with poor prognosis.
• BASP1 knockdown suppresses GC cell proliferation, migration, and invasion while promoting apoptosis.
• m6A modification regulates BASP1 stability, with IGF2BP2 identified as a key regulator.
• BASP1 promotes IL6 secretion and M2 macrophage polarization through the PI3K/AKT pathway.
• BASP1 overexpression in vivo enhances tumor growth and increases M2 macrophage infiltration and IL6 levels.

Conclusions:

• BASP1 plays a significant role in GC progression and modulates the tumor microenvironment.
• The findings elucidate the mechanism by which BASP1 influences GC via IL6, M2 macrophages, and the PI3K/AKT pathway.
• Targeting BASP1 presents a promising therapeutic avenue for gastric cancer treatment.