BMI1 expression

In conclusion, LiCl can ameliorate cisplatin ototoxicity by elevating BMI1 expression through activation of the Wnt/β-catenin pathway. Overexpression of BMI1 inhibits the Wnt/β-catenin pathway and reduces cisplatin-induced hair cell damage.

In summary, we found that KGF secreted by HSCs activated PAK4, which phosphorylated S315 and promoted protein stability of BMI1, and further promoted liver fibrosis and HCC stemness through the PI3K/AKT signaling pathway. Our present study deeply studied the interaction and mechanism between HSCs and HCC, which might provide a new insight for HCC therapy.

Further studies will illuminate the role that BMI1 plays in ocular cells. BMI1 levels are lower in aged retinas, possibly reflecting changes in retinal somatic and stem cell maintenance and disease susceptibility.

Moreover, we evaluated the therapeutic potential of a BMI1 inhibitor in combination with Bevacizumab for NSCLC treatment using orthotopic models. The data presented in our study reveal a previously unrecognized role of the SOX4-BMI1 axis in promoting NSCLC progression and angiogenesis. This research significantly contributes to our knowledge of the interplay between SOX4 and BMI1 in NSCLC, potentially paving the way for the development of targeted therapies for this disease.

These findings suggest that GA is a potential candidate for targeting GSCs and therefore be used to treat GBM.

Concomitantly, Ab-ECSnps showed neurotherapeutic potential in the in vivo PD model. We showed for the first time that our brain-specific targeted delivery might regulate calpain-mediated BMI1 expression, thereby preserving mitochondrial homeostasis to alleviate PD.

We previously developed a transgenic mouse model (KrTB) containing a doxycycline- (dox) controlled, Tet-responsive element system to selectively overexpress Bmi1 in the tongue basal epithelial SCs...Finally, using a human oral keratinocyte line (OKF6-TERT1R), we showed that ectopic Bmi1 overexpression decreases the oxygen consumption rate while increasing the extracellular acidification rate, indicative of elevated glycolysis. Thus, our data demonstrate that high Bmi1 expression drives hypoxic signaling, including metabolic reprogramming, in normal oral cavity epithelia.

In addition, miR-539-3p overexpression reversed the protective effects of CCAT2. Furthermore, CCAT2 activated the Wnt/β-catenin pathway under the H/R condition via the miR-539-3p/BMI1 axis.Overall, this investigation showed the protective effects of the CCAT2/miR-539-3p/BMI1/Wnt/β-catenin regulatory axis against cardiomyocyte injury induced by H/R.

The colitis group treated with the highest dose of vitamin D3 (0.6 mcg/25 gram) showed the lowest MCHI score (3.60±0.64) while the lowest dose of vitamin D3 had the highest MCHI score (12.60±1.47). In conclusion, by stimulating stem cells, vitamin D3 administration stimulates mucosal regeneration, as demonstrated by upregulated expression of Lgr5-Bmi-1.

Analysis of the difference between these cell lines revealed that Myc activity plays a pivotal role in SET KD-mediated Bmi-1 degradation. Our data added new insights into the molecular mechanism of the SET-regulated colony-forming ability, in which Akt-mediated activation of mTORC1/p70S6K and Bmi-1 signaling.

Our study provided evidence that miR-128-mediated silencing of BMI-1 could prevent malignant progression of GIST, highlighting a promising anti-tumor target for combating GIST.

Mechanistically, BMI1 epigenetically up-regulates CTSB secretion in TICs by repressing miR-218-1-3p expression. These findings identify a potential diagnostic and therapeutic target for HCC patients with BDTT.

HBV-associated proliferative HCC might be related to the HBsAg-YAP-BMI1 axis and offer a potential target for the development of new therapeutic approaches.

High expression of BMI-1 in liver cells is associated with CRLM progression. BMI-1 activates HSCs to secrete factors to form a prometastatic environment in the liver, and aHSCs promote proliferation, migration, and the EMT in CRC cells partially through the TGF-β/SMAD pathway.

When expression of Bmi-1 was up-regulated as a result of H.pylori infection or pLPCX-Bmi-1 transfection, the GES-1 cells had higher invasiveness and lower apoptosis rate with the above treatment respectively. Conclusion H. pylori infection can inhibit the apoptosis of gastric cancer cells and promote their invasion via up-regulating expression of Bmi-1.

Immunohistochemistry and quantitative real-time PCR analyses revealed that HRY expression correlated positively with Bmi-1 expression in a cohort of NPC biopsies. These findings suggested that HRY promotes NPC cell stemness by upregulating Bmi-1, and that silencing Bmi-1 can suppress NPC progression.

Taken together, the findings of our study suggest that Sox18 mediates the resistance of Bmi1-expressing cells to cetuximab in HNSCC via the oxidative phosphorylation pathway.

Furthermore, α-tocopherol restored sperm count (Ctrl vs. PTC-209, p = 0.0034; Ctrl vs. PTC-209 + α-tocopherol, p = 0.7293) and normalized sperm malformation such as broken heads, irregular heads, lost and curled tails in vivo, as demonstrated by its antagonism with the BMI1 inhibitor PTC-209. Analysis demonstrated that α-tocopherol is a potent in vitro and in vivo modulator of BMI1, a transcription factor that plays an important role in in SSC proliferation and spermatogenesis. Our findings identify a new target and strategy for treating male infertility that deserves further pre-clinical investigation.

Our study demonstrates that BMI-1 affects the cellular activity, proliferation, migration, and invasion of GC cells. Silencing the BMI-1 gene significantly reduces the number of SP cells and the expression of drug-resistant proteins in ADR-treated GC cells. We speculate that inhibition of BMI-1 increases the drug resistance of GC cells by affecting GCSCs, and that EZH2, CBX8, CBX4, and SUZ12 may participate in BMI-1-induced enhancement of GCSC-like phenotype and viability.

Collectively, our results validate the use of ALX bis-biguanide to potentiate the action of conventional TKI treatment as a potential new therapeutic solution to eradicate CML LSCs.

Therefore, elucidating the functional role of Bmi-1 in CSC-mediated cancer progression may unveil an attractive target for mechanism-based, developmental therapeutics. In this review, we discuss the parallels in the role of Bmi-1 in stem cell biology of health and disease and explore how this can be leveraged to advance clinical treatment strategies for head and neck cancer.

Moreover, a significant positive correlation between Bmi-1 and SUVmax was observed in GAC tissues. In conclusion, our findings demonstrate a novel correlation between Bmi-1 and preoperative SUVmax in GAC patients who did not receive radiotherapy, chemotherapy, or targeted treatment before surgery, and both are positively correlated with unfavorable prognostic factors and a higher grade of malignancy.

14-Deoxy-11,12-dehydroandrographolide (18) was highly cytotoxic to DU145 cells with an IC value of 25.4 µM. Western blotting analysis of compound 18 in DU145 cells suggested that compound 18 suppresses BMI1 expression.

miR-203a may serve as a crucial treatment target in HBsAg-positive HCC. More explicit mechanistic studies and animal experiments need to be conducted as a next step.

In conclusion, DSF/copper targets CSCs in DTCs by inhibiting c-Myc- or E2F1-mediated BMI1 expression. Therefore, DSF is a potential therapeutic agent for future therapy in DTCs.

miR-3682-3p promoted HCC migration and stemness through PTEN/PI3K/AKT/β-catenin signaling, implying that miR-3682-3p might be a promising target for HCC clinical treatment.

Collectively, these results demonstrate that p53 defines the stemness of MEC and suggest that therapeutic activation of p53 might have clinical utility in patients with salivary gland mucoepidermoid carcinoma.

RNA immunoprecipitation, actinomycin D assay and western blot assays suggested that SNHG3 could also bind c-MYC protein which subsequently facilitate the stabilization of BMI1 mRNA, thus enhancing BMI1 protein level...Overall, this study has provided new insights into the potential implication of lncRNA SNHG3 in the pathogenesis of BLCa. Importantly, SNHG3/c-MYC/BMI1 axis may be a novel target for regulating tumor growth and metastasis in BLCa patients.

These data demonstrate the relevance of the better understanding of the interaction between HNCSCs and immune cells in the tumor microenvironment. The ultimate clinical implication is to ground the choice of optimized targets and improve immune recognition for ongoing treatments as well as the response to approved immunotherapies.

BMI1 is an unfavorable prognostic biomarker of CCA. Our data depict a novel function of BMI1 in CCA tumorigenesis and metastasis mediated by exosomes. Besides, BMI1 inhibition may augment immune checkpoint blockade to inhibit tumor progression by activating cell-intrinsic immunity of CCA.

A novel small-molecule, BI-44, was developed, which effectively suppressed BMI1/MCL1 expressions and inhibited tumour formation and progression in preclinical models. Targeting cancer stemness mediated by BMI1/MCL1 with BI-44 provides the basis for a new therapeutic approach in NSCLC treatment.

We speculate that GLI1 and related proteins play an important role in regulating the proliferation and differentiation of tumors. Therefore, it provides important reference for the pathogenesis and pathogenicity of canine mammary tumor.

Our results suggest that the previously unreported Bmi1-UPF1-HK2 pathway contributes to PC progression and immunosuppression, which may bring in new targets for developing effective therapies to treat PC patients.

The BMI1 inhibitor, PTC-209, suppressed BMI1 expression in established canine glioma cell lines and resulted in antiproliferative activity when used alone and in combination with chemotherapeutic agents...PTC-209 targeting of BMI1 activated the RB pathway through downregulation of total and phosphorylated RB, independent of INK4A/ARF signaling, likely through BMI1-inhibition mediated upregulation of p21. These data support the rationale for targeting of BMI1 signaling and the use of canine glioma as a translational therapeutic model for human disease.

Our data demonstrate that ErbB3 regulates Bmi1 expression through PI3K/Akt and MAPK signaling in both human and mouse intestinal cells. Furthermore, BMI1 activity promotes LYZ1 expression. Together, these results support our hypothesis that ErbB3 regulates secretory cell differentiation through BMI1 in the intestinal epithelium.

The levels of MMP2, MMP7, MMP9, Rock1, RhoA and p53, p21, Bax protein in BMI1 overexpression group were significantly increased, while the levels of MMP2, MMP7, MMP9, Rock1, RhoA and p53, p21, Bax protein in BMI1 inhibitor group were significantly decreased. BMI1 is highly expressed in endometrial cancer tissues, and inhibiting BMI1 expression can reduce the proliferation, migration, and invasion of HEC-1B cells after ionizing radiation and promote apoptosis, which offers new insights into the clinical radiotherapy of tumors.

Further mechanistic analysis indicated that protection effects of RES was relative with Bmi-1. This is the first study on the role of Bmi-1 in the pathogenesis of NAFLD and the target of resveratrol against NAFLD.

Our bioinformatics analysis suggested that the BMI1 multifunctionality is determined by its high level of intrinsic disorder that defines the ability of this protein to bind to numerous cellular partners. These results demonstrate a close relationship between BMI1 expression and mitochondrial health in hyperoxia-induced acute lung injury (HALI) and indicate that BMI1 is a potential therapeutic target to treat ALI and Acute Respiratory Distress Syndrome.

Cell viability was significant decreased in response to carboplatin in HGSC cells TYK-nu and OVHASO, and in mOC cell lines COV644 and EFO-27. Western blot analysis demonstrated various expression levels across all cell lines. BMI-1 could be a useful potential therapeutic target in some ovarian cancer patients, including mOC patients.

The up-regulation of Bmi-1 expression promotes the malignant biological behavior of OL cells. Bmi-1 expression can be used as a predictor for malignant transformation of OL.

Moreover, an overexpression of BMI1 in HBECs reduced the SiO-senescenced cells, enhanced the potency of cell proliferation and differentiation, and increased capacity of airway epithelial regeneration in response to the persistent exposure of SiO. These data suggest that Bmi1 is a key transcription factor engaging in maintaining the self-renewal, proliferation and differentiation of epithelial stem cells in lung during the development of silicosis disease.