Sirna-Mediated Silencing of Placenta-Specific Protein 1 (Plac1) Alters Cd4+, Cd8+, and Regulatory T Cells in a Murine Colon Cancer Model Publisher Pubmed



Esparvarinha M ; Nickho H ; Najafi A ; Keykhaee M ; Mehrabadi A Z ; Aghebati Maleki L ; Falak R ; Yousefi M
Source: Scientific Reports Published:2026

Abstract

PLAC1 has been found to be upregulated in colorectal cancer (CRC). However, its precise role and the molecular mechanisms driving CRC progression remain unclear. This study aimed to elucidate the role of PLAC1 in CRC progression and to evaluate its immunomodulatory effects using an in vivo syngeneic mouse model. Small interfering RNA (siRNA) was employed to silence PLAC1 expression in the CT26 murine colorectal cancer cell line. Gene silencing efficiency was confirmed by quantitative real-time PCR (qRT-PCR). CT26 cells were subcutaneously injected into BALB/c mice to establish an in vivo tumor model. Tumor growth was monitored, and immune responses were assessed by analyzing tumor-infiltrating lymphocytes (TILs) and splenic immune cell populations. Flow cytometry was used to characterize T cell subsets (CD3, CD4, CD8, FoxP3) and PLAC1 expression. PLAC1 knockdown was associated with a reduction in the frequency of regulatory T cells (Tregs) in both tumor and spleen. It was also associated with an increased proportion of CD3⁺CD4⁺ T cells in the spleen and CD3⁺CD8⁺ T cells in the tumor. Intratumoral administration of PLAC1-targeting siRNA was associated with reduced tumor volume, extended survival, and was associated with changes consistent with enhanced antitumor immunity in tumor-bearing mice. Silencing of PLAC1 was associated with decreased Treg frequency and increased effector T cell populations, suggesting a shift toward a less immunosuppressive tumor microenvironment. These findings may support further investigation of PLAC1 as a potential target for immunotherapeutic strategies in CRC and other malignancies expressing PLAC1. © The Author(s) 2026.