Targeting Siglec-15 mediates mitochondrial retrograde regulation of cervical cancer development.

Cervical cancer (CCA) is the predominant cause of fatalities from gynecologic malignancies, with metastasis responsible for 80 % of cancer-related mortalities. This study preliminarily examined the involvement of Sialic Acid Binding Ig Like Lectin 15 (Siglec-15) in the development of CCA and its probable mechanisms. We assessed the capacity of Siglec-15 to modulate CCA progression by establishing knockdown and overexpression Siglec-15 cell lines, supplemented with animal models, using both in vivo and in vitro dual investigations. Our findings indicate that Siglec-15 is significantly expressed in CCA cell lines and is intimately associated with the proliferation, migration, and invasion capabilities of CCA cells, as well as mitochondrial ROS homeostasis. The suppression of Siglec-15 expression markedly reduced tumor growth in mice, potentially due to Siglec-15's role in regulating the Mitogen-Activated Protein Kinase (MAPK) signaling pathway, which mediates the retrograde regulation of mitochondrial ROS homeostasis. Siglec-15 may emerge as a novel therapeutic target and prognostic marker for patients with CCA.