A ring finger protein called B-cell-specific Moloney leukemia virus insertion site 1 (BMI1) is an unfavorable prognostic factor in cholangiocarcinoma (CCA), found a new study published in the journal Cellular and Molecular Life Sciences.
Inhibiting the protein could increase immune checkpoint blockade, thereby inhibiting tumor progression, according to the authors of the study.
The prognosis of CCA is very poor, with a 5-year survival rate of only 10% due to the difficulty of early diagnosis and few treatment options available especially once the disease has progressed. It is therefore of great importance to identify biomarkers that can help identify the disease early.
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It is already known that BMI1 is dysregulated in many types of cancers but its exact role and prognostic value in CCA are not well understood.
Read more about the prognosis of CCA.
Here, a team of researchers from China investigated the clinical importance and potential role of BMI1 in CCA prognosis. They measured the expression of BMI1 in 930 patients with CCA who underwent surgical resection from 2010 to 2020 at Qilu Hospital of Shandong University to treat their disease.
They found that BMI1 was substantially upregulated in cancerous tissues and showed that it was an independent prognostic biomarker for the disease.
Using a CCA cell line, the researchers showed that BMI1 overexpression promotes cell proliferation, migration, and invasion. When they knocked down the protein, the team saw that the proliferation and metastasis of the disease were inhibited both in vitro and in vivo.
“Interestingly, we found that CCA-derived exosomes contain BMI1 proteins, which can transfer BMI1 between CCA cells,” the researchers said. They demonstrated that exosomes containing BMI1 promoted proliferation and metastasis through autocrine and paracrine mechanisms.
Finally, they showed that BMI1 promotes H2A ubiquitination in CCA cells, thereby inhibiting chemokines that normally recruit CD8+ T cells to the site of the tumor.
“Our study demonstrates an underlying mechanism of CCA development and provides a new combination therapy strategy suppressing CCA proliferation and metastasis,” the authors concluded.
Reference
Liu Z, Hu C, Zheng L, et al. BMI1 promotes cholangiocarcinoma progression and correlates with antitumor immunity in an exosome-dependent manner. Cell Mol Life Sci. 2022;6;79(9):469. doi:10.1007/s00018-022-04500-1
