MORC2 facilitates cholangiocarcinoma progression through cell cycle acceleration and immune microenvironment modification.

Abstract

This study explored a novel therapeutic target, MORC2 (Microrchidia family CW-type zinc finger 2), for patients with unresectable advanced Cholangiocarcinoma (CCA), a lethal epithelial cell malignancy lacking effective treatments. Utilizing bioinformatics analysis, we examined MORC2's role in CCA progression. The focus was on its association with the cell cycle and its involvement in the tumor's immunosuppressive microenvironment. MORC2 was found to accelerate CCA cell proliferation by promoting cell cycle progression through the activation of TNF-α signaling via the NFKB signaling pathway. Furthermore, the downregulation of MORC2 induced cell cycle arrest and might facilitate neutrophil infiltration by upregulating CCL3, indicating its pivotal role in modifying the immunosuppressive tumor microenvironment. Our findings suggest that MORC2 plays a crucial role in both the proliferation of CCA cells and the modification of the tumor microenvironment. Targeting MORC2 presents a novel potential therapeutic approach for patients with advanced CCA.