Thus, inhibition of BMI1 expression particularly in breast cancer stem cells can be used as a potential strategy for the complete elimination of tumor and to prevent disease relapse.
Regulation of B cell-specific Moloney murine leukaemia virus integration site 1 (BMI1) expression with increase in histological grades of breast carcinoma in correlation with hormone receptor status was studied in 60 Indian breast cancer patient's formalin-fixed paraffin-embedded tissue blocks.
We also show that PTC-209, a small molecule inhibitor of BMI1 gene expression induces cellular senescence and transcriptionally upregulates expression of miR-200c/141 cluster in breast cancer cells.
These results show that inhibiting Bmi1 expression in breast cancer stem cells could be important for the complete elimination of tumor and potentially preventing disease relapse.
Here we have made an endeavor to search whether any miRNAs are involved in the regulation of BMI1 in breast cancer that leads to mitochondrial dependent apoptotic cell death.
Our data shows that PHGDH deficiency impairs the tumorsphere formation capacity in embryonal carcinoma stem-like cells (ECSLCs), breast cancer stem-like cells (BCSLCs) and patient-derived brain tumor-initiating cells (BTICs), which is accompanied by the reduced expression of characteristic stemness-promoting factors, such as Oct4, Nanog, Sox-2, and Bmi-1.
Bmi-1 mRNA is significantly up-regulated in adjacent normal breast tissue in breast cancer patients compared to normal breast tissue from noncancerous patients.
With a series of biology approaches, subsequently, we proved that BMI1 was a functional downstream target of miR-630 and mediated the property of miR-630-dependent inhibition of breast cancer progression.
In the present study, we further demonstrated that 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), an inhibitor of Hsp90, could suppress the self-renewal of BCSCs by downregulating B lymphoma Mo-MLV insertion region 1 homolog (BMI1), a polycomb family member with oncogenic activity in breast cancer.
Bmi-1 was expressed in 53.2% of breast cancer patients by immunohistochemistry, and the expression of Bmi-1 was significantly correlated with favorable prognostic indices at diagnosis.
Thus, our study suggests a cross-talk between Bmi1 and miR-200c mediated by p53, and Bmi1 interference would improve chemotherapy efficiency in breast cancer via susceptive apoptosis induction and cancer stem cell enrichment inhibition.
These results indicate that Bmi-1 may play an important role in radiosensitivity, and the suppression of its expression might be a potential therapeutic target for breast cancer.
Polycomb group (PcG) protein BMI1 is an important regulator of oncogenic phenotype and is often overexpressed in several human malignancies including breast cancer.
This study not only bridges the missing link between stem cell-related transcription factor (Bmi1) and ABC transporter (ABCC5) but also contributes to development of potential therapeutics against breast cancer.
Our data suggest that the oncogenic role of Bmi-1 in human primary breast carcinomas is not determined by its capacity to inhibit INK4a/ARF proteins or to induce telomerase activity.