BMI1 Roles in Cancer Stem Cells and Its Association with MicroRNAs Dysregulation in Cancer: Emphasis on Colorectal Cancer

Soheilifar, Mohammad Hasan; Moshtaghian, Abdolvahab; Maadi, Hamid; Izadi, Fereshteh; Saidijam, Massoud

doi:10.5812/ijcm.82926

Cited by 7 publications

(8 citation statements)

References 81 publications

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“…In silico analysis and in vitro selection revealed that miR-1291 was an upstream modulator of DCLK1. miR-1291 also decreased the expression of CSC markers BMI1 and CD133, but scarcely decreased CD166 expression (25,26,68,74). Since these molecules are not likely to be direct targets of miR-1291 according to TargetScan predictions, it is postulated that the decrease in BMI1 and CD133 may reflect certain diminution of the stem-like properties of HCT116 cells, which could be an indirect effect of miR-1291 through DCLK1.…”

Section: Discussionmentioning

confidence: 99%

“…CSCs confer resistance to anticancer drugs and radiotherapy, and thus cause distant metastases and recurrence ( 22 - 24 ). Several CSC markers for CRC have been identified, including CD133, B cell-specific Moloney murine leukemia virus integration site 1 (BMI1) and leucine rich repeat containing G protein-coupled receptor 5 ( 23 , 25 , 26 ). Previously, doublecortin-like kinase 1 (DCLK1) was demonstrated to be a CSC marker in CRC ( 27 , 28 ).…”

Section: Introductionmentioning

confidence: 99%

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Functional assessment of miR‑1291 in colon cancer cells

et al. 2022

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miR-1291 exerts an anti-tumor effect in a subset of human carcinomas, including pancreatic cancer. However, its role in colorectal cancer (CRC) is largely unknown. In the present study, the expression and effect of miR-1291 in CRC cells was investigated. It was identified that miR-1291 significantly suppressed the proliferation, invasion, cell mobility and colony formation of CRC cells. Additionally, miR-1291 induced cell apoptosis. A luciferase reporter assay revealed that miR-1291 directly bound the 3'-untranslated region sequence of doublecortin-like kinase 1 (DCLK1). miR-1291 also suppressed DCLK1 mRNA and protein expression in HCT116 cells that expressed DCLK1. Furthermore, miR-1291 suppressed cancer stem cell markers BMI1 and CD133, and inhibited sphere formation. The inhibitory effects on sphere formation, invasion and mobility in HCT116 cells were also explored and verified using DCLK1 siRNAs. Furthermore, miR-1291 induced CDK inhibitors p21 WAF1/CIP1 and p27 KIP1 in three CRC cell lines, and the overexpression of DCLK1 in HCT116 cells led to a decrease of p21 WAF1/CIP1 and p27 KIP1 . Intravenous administration of miR-1291 loaded on the super carbonate apatite delivery system significantly inhibited tumor growth in the DLD-1 xenograft mouse model. Additionally, the resultant tumors exhibited significant upregulation of the p21 WAF1/CIP1 and p27 KIP1 protein with treatment of miR-1291. Taken together, the results indicated that miR-1291 served an anti-tumor effect by modulating multiple functions, including cancer stemness and cell cycle regulation. The current data suggested that miR-1291 may be a promising nucleic acid medicine against CRC.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Functional assessment of miR‑1291 in colon cancer cells

et al. 2022

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“…miR-125b and miR-128, two of the major miRNAs described to be downregulated in GBM, show a remarkably lower expression in CD133+ GSCs, as compared with CD133-cell populations. Upon expression, they both inhibit GBM growth by decreasing the self-renewal and proliferation of GSCs, via BMI1 Proto-Oncogene, Polycomb Ring Finger (BMI-1) downregulation, thereby exerting a pro-apoptotic role [65,66,67,68,69,70,71]. Moreover, miR-128 represses GSCs growth and mediates their differentiation by targeting the oncogenic EGFR/Platelet-Derived Growth Factor Receptor/AKT Serine/Threonine Kinase (EGFR/PDGFR/AKT) signaling [68,72,73].…”

Section: Mirnas In Human Neural Cscsmentioning

confidence: 99%

MicroRNA Signature in Human Normal and Tumoral Neural Stem Cells

Diana

Gaido²,

Murtas

2019

IJMS

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MicroRNAs, also called miRNAs or simply miR-, represent a unique class of non-coding RNAs that have gained exponential interest during recent years because of their determinant involvement in regulating the expression of several genes. Despite the increasing number of mature miRNAs recognized in the human species, only a limited proportion is engaged in the ontogeny of the central nervous system (CNS). miRNAs also play a pivotal role during the transition of normal neural stem cells (NSCs) into tumor-forming NSCs. More specifically, extensive studies have identified some shared miRNAs between NSCs and neural cancer stem cells (CSCs), namely miR-7, -124, -125, -181 and miR-9, -10, -130. In the context of NSCs, miRNAs are intercalated from embryonic stages throughout the differentiation pathway in order to achieve mature neuronal lineages. Within CSCs, under a different cellular context, miRNAs perform tumor suppressive or oncogenic functions that govern the homeostasis of brain tumors. This review will draw attention to the most characterizing studies dealing with miRNAs engaged in neurogenesis and in the tumoral neural stem cell context, offering the reader insight into the power of next generation miRNA-targeted therapies against brain malignances.

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“…BMI‐1 is involved in different pathways, including axial patterning, hematopoiesis, cell cycle regulation, and senescence [13]. Furthermore, besides its roles during development, BMI‐1 expression faces alterations in different cancer types, including CRC and then could be considered as an oncogene [14, 15].…”

Section: Introductionmentioning

confidence: 99%

Assessment of clinicopathological and prognostic relevance of BMI‐1 in patients with colorectal cancer: A meta‐analysis

Pourjafar

Samadi

Karami

et al. 2020

Biotechnology and Applied Biochemistry

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B‐cell‐specific Moloney leukemia virus insertion site 1 (BMI‐1) is one of the stemness markers. The prognostic and clinicopathological effects of BMI‐1 expression in colorectal cancer (CRC) have been in dispute with different studies. Eligible studies were retrieved from international databases up to December 2019. Studies with a relationship between the clinicopathological and prognostic value of CRC patients with BMI‐1 expression were selected. The correlations in the random‐effect model were evaluated using the hazard ratios, odds ratio, and 95% confidence intervals (CIs). A total of nine studies comprising Asian cases (seven studies) and European cases (two studies) covering 1,294 samples of CRC were included for this meta‐analysis. The analysis suggested that in Asian cases, increased expression of BMI‐1 was associated with poor overall survival (OS) and death‐free survival, whereas in European populations, high expression of BMI‐1 was associated with better OS. Also, overexpression of BMI‐1 in the Asian population was associated with the tumor size, distant metastasis, and patient's gender and age. Results suggested that high expression of BMI‐1 can be involved in the progression and invasion of CRC, and so its inhibitor‐based therapies could be used to prevent the progression of CRC.

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BMI1 Roles in Cancer Stem Cells and Its Association with MicroRNAs Dysregulation in Cancer: Emphasis on Colorectal Cancer

Cited by 7 publications

References 81 publications

Functional assessment of miR‑1291 in colon cancer cells

Functional assessment of miR‑1291 in colon cancer cells

MicroRNA Signature in Human Normal and Tumoral Neural Stem Cells

Assessment of clinicopathological and prognostic relevance of BMI‐1 in patients with colorectal cancer: A meta‐analysis

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