OSBPL3 promotes colorectal cancer progression through modulation of TGF-β signaling and immune cell infiltration

Colorectal cancer (CRC) is the third most common cancer worldwide, with prognosis often limited by disease progression. The role of oxysterol-binding protein-like 3 (OSBPL3) in various cancers remains unclear. This study aimed to investigate the expression, biological function, and relationship of OSBPL3 with the tumor microenvironment (TME) in CRC, and to assess its potential as a therapeutic target.

We employed bioinformatic analysis, immunohistochemistry (IHC), Cell Counting Kit-8 (CCK-8) assay, Western blot (WB), ethynyl deoxyuridine (EdU) incorporation assay, wound healing assay, transwell assay, and animal models to characterize the expression pattern of OSBPL3 in CRC. We assessed the effects of OSBPL3 on CRC cell proliferation, migration, invasion, and apoptosis. Additionally, we investigated the mechanisms by which OSBPL3 drives CRC progression through the TGF-β signaling pathway and immune cell infiltration.

OSBPL3 was highly expressed in CRC, and its elevated expression was positively correlated with lymphatic metastasis. High OSBPL3 expression was associated with activity of the TGF-β signaling pathway and with epithelial-mesenchymal transition (EMT). Cellular experiments and animal models demonstrated that OSBPL3 knockdown suppressed CRC cell proliferation, migration, and invasion and increased apoptosis, whereas OSBPL3 overexpression produced the opposite effects. Furthermore, OSBPL3 knockdown inhibited TGF-β signaling and EMT, while OSBPL3 overexpression showed the reverse pattern. Additionally, OSBPL3 expression was positively correlated with central memory T cells (Tcm) and Th2 cells but negatively correlated with regulatory T cells (Tregs).

OSBPL3 expression is positively associated with increased proliferative and invasive capacities of CRC cells. Our analyses further indicate that OSBPL3 is closely linked to TGF-β/SMAD signaling activity, EMT-related molecular features, and the immune infiltration landscape within the TME. Collectively, these findings suggest that OSBPL3 may serve as a clinically relevant biomarker and a potential therapeutic target in CRC.