Regulation of gene transcription of B lymphoma Mo‑MLV insertion region 1 homolog (Review)

Abstract

B lymphoma Mo-MLV insertion region 1 homolog (Bmi-1) is a core protein component of the polycomb repressive complex 1 that inhibits cell senescence and maintains the self-renewal ability of stem cells via downregulation of p16Ink4a and p19Arf expression. Bmi-1 serves an important role in hematopoietic stem cell maintenance and neurodevelopment during embryonic development, and it has been shown to enhance tumorigenesis by promoting cancer stem cell self-renewal and epithelial to mesenchymal transition. Emerging evidence suggests that Bmi-1 overexpression is closely related to the development and progression of various types of cancer, and that downregulation of Bmi-1 expression can inhibit the proliferation, invasion and metastasis of cancer cells. It is therefore important to elucidate the mechanisms underlying the regulation of Bmi-1 expression both under normal growth conditions and in malignant tissues. In the present review, the current body of knowledge pertaining to the transcriptional and post-transcriptional regulation of the BMI-1 gene is discussed, and the potential mechanisms by which Bmi-1 is dysregulated in various types of cancer are highlighted. Bmi-1 expression is primarily controlled via transcriptional regulation, and is regulated by the transcription https://www.ushuaia.pl/hyphen/?ln=en factors of the Myc family, including Myb, Twist1, SALL4 and E2F-1. Post-transcriptionally, regulation of Bmi-1 expression is inhibited by several microRNAs and certain small-molecule drugs. Thus, regulatory transcriptional factors are potential therapeutic targets to reduce Bmi-1 expression in cancer cells. Thus, the present review provides an up-to-date review on the regulation of BMI-1 gene expression at the transcriptional and post-transcriptional level.

miRNA Profiling of Hungarian Regressive Wilms’ Tumor Formalin-Fixed Paraffin-Embedded (FFPE) Samples by Quantitative Real-Time Polymerase Chain Reaction (RT-PCR)

“…Downregulation of miR-194-5p by Wilms’ tumor tissue is needed for cell migration and invasion (ie, metastasis) [ 37 ]. Some other known targets of miR-194-5p are BMI1 [ 38 ] and IGF1R (insulin-like growth factor 1 receptor) [ 39 ], accounting for its tumor-suppressor role in many other cancer types ( Figure 1 ). Previously, we found the underexpression of this miRNA as seen in blastemal FFPE samples to be well in line with data in the literature obtained from snap-frozen tissue or peripheral blood [ 11 ].…”

Natural Compounds with BMI1 Promoter Inhibitory Activity from <i>Mammea siamensis</i> and <i>Andrographis paniculata</i>

“…One new coumarin (1) and 15 known compounds (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17) were isolated from M. siamensis, guided by BMI1 promoter inhibitory activity. Coumarin derivatives 2 and 4-12 suppresses the BMI1 promoter and compound 5 shows strong cytotoxicity against Huh7 and HCT116 cells.…”

“…The Ink4a/ARF gene induces cell cycle regulators and the tumor suppressor p14ARF gene, causing cell cycle arrest or apoptosis. [3][4][5] BMI1 is an essential self-renewal regulator for multiple stem cell systems, such as hematopoietic, nerves, and breast stem cells, and BMI1 is also highly expressed in various tumor tissues. 6,7) Especially, BMI1 is known to be highly expressed in cancer stem cells (CSCs) that contribute to cancer recurrence and metastasis due to their resistance to chemotherapy and radiation therapy.…”