For the first time, we provide images of human prostate carcinoma metastasis precursor cells isolated from blood and shown to overexpress both BMI1 and Ezh2 oncoproteins.
Moreover, immunohistochemical staining revealed Bmi-1 was overexpressed in 63.2% UCC tissues (Bmi-1 ++ or +++), and the overexpression of Bmi-1 protein was significantly correlated with tumor size (P = 0.046), clinical stage (P = 0.021), and regional lymph nodes metastasis (P = 0.010).
These findings demonstrate the novel mechanism for BMI-1 in contributing to EC cell invasion and that repression of BMI-1 by miR-194 could have a therapeutic potential to suppress EC metastasis.
The high expression of BMI-1 in cervical cancer is related to tumor progression, lymph node metastasis and HPV infection, suggesting that cervical cancer with excessive BMI-1 expression possesses high metastases potential and that BMI-1 may be a promising biomarker for predicting metastasis in cervical cancer.
In addition, miR-200c overexpression significantly inhibited melanoma xenograft growth and metastasis in vivo, and this correlated with diminished expression of BMI-1 and reduced levels of E-cadherin in these tumors.
Elevated Bmi1 is associated with cervical node metastasis, Ki-67 abundance and reduced overall survival, and also serves as an independent prognostic factor for patient outcomes.
These results suggest that Bmi-1 is a key gene in regulation of EMT and migration of breast cancer cells induced by IR through activation of PI3K/AKT signaling; therefore, Bmi-1 could be a new target for inhibiting metastasis caused by IR.
Our study implies that detection of Bmi-1 and RKIP is valuable in predicting patient survival and therapeutic response in gastric cancer, and the inverse association between Bmi-1 and RKIP reveals the potential molecular mechanisms underlying tumor metastasis and chemotherapy resistance.
Taken together, our findings disclose for the first time that Bmi-1 level accumulates strongly in early stage and then declines in late stage, which is potentially important for NSCLC cell invasion and metastasis during progression.
Suppression of endogenous miR-429 promoted cell growth and metastasis. miR-429 was shown to directly target the 3' untranslated regions of B-cell-specific Moloney murine leukemia virus insertion site 1 (BMI1) and E2F transcription factor 3 (E2F3) transcripts, regulating their expression, as well as that of the downstream epithelial-to-mesenchymal transition markers E-cadherin, N-cadherin, vimentin, p14, and p16.
But high Bmi1 expression was significantly correlated with the clinical stage (pooled OR=3.04, 95%CI=1.31-7.07, P=0.010, random effect), tumor size (pooled OR=2.01, 95%CI=1.14-3.55, P=0.016, random effect), T classification (pooled OR=2.79, 95%CI=1.94-4.03, P<0.001, fixed effect), lymph node metastasis (pooled OR=2.24, 95%CI=1.47-3.39, P<0.001, random effect) and distant metastasis (pooled OR=5.05, 95%CI=1.29-19.70, P=0.020, random effect), and led to a poor overall survival (OS) in GC patients (RR=3.38, 95%CI=2.43-4.69, P<0.001, fixed effect).
In the current study, a relatively lower miR-452 and higher BMI1 expression levels were confirmed to be associated with advanced tumor stage and more extent of lymph nodes metastasis.
The B-cell-specific Moloney leukemia virus inset site 1 gene (BMI-1) has attracted considerable attention in recent years because of its key role in breast cancer development and metastasis.
These data yield key insights into melanoma biology and establish BMI1 as a compelling drug target whose inhibition would suppress both metastasis and chemoresistance of melanoma.
Finally, we identified that BMI-1 expression activating PI3K/AKT singing pathway by negative regulating PTEN was the main mechanism of promoting invasion and metastasis ability of pancreatic CSCs.
It is known that epithelial-mesenchymal transition and stemness transcription factors (TWIST1, SNAI2/SLUG, and BMI1) play an important role in metastasis and their dysregulation has been demonstrated in metastatic cancers.
Compounding a previously described Bmi1-transgene and Pten-deficiency prostate cancer mouse model with the Ezh2 transgene did not enhance tumour progression or drive metastasis formation.
Putative cancer stem cells (CSCs) have been identified in HNSCC, and BMI1 expression has been linked to these phenotypes, but optimal treatment strategies to overcome chemotherapeutic resistance and eliminate metastases have not yet been identified.
(2017) show that mouse and human HNSCCs and their metastases depend on Bmi1-expressing cancer stem cells and AP1 signaling and that simultaneously inhibiting Bmi1 or AP1, combined with Cisplatin, reduces tumor growth effectively in preclinical models.
The results showed that Bmi-1 was significantly associated with tumor size (n = 7, OR = 1.79, 95% CI = 1.19-2.71, P = .005, fixed effect), poor differentiation (OR = 1.61, 95% CI = 1.11-2.33, P = .011, fixed effect), and distant metastasis (n = 4, OR = 4.69, 95% CI = 1.52-14.41, P = .007, fixed effect).