PLK1 Inhibition Down-regulates Polycomb Group Protein BMI1 via Modulation of the miR-200c/141 Cluster

Dimri, Manjari; Cho, Joon-Ho; Kang, Mingu; Dimri, Goberdhan P.

doi:10.1074/jbc.m114.615179

Cited by 21 publications

(25 citation statements)

References 51 publications

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Section: Resultsmentioning

confidence: 99%

“…We recently showed that both miR-200c and miR-141 can target BMI1 [28]. We have also reported that an indirect inhibition of BMI1 by PLK1 inhibitor can lead to upregulation of miR-200c/141 cluster [28], suggesting that BMI1 may directly regulate it via an autoregulatory loop similar to the reciprocal regulation of ZEB1 and miR-200c/141 cluster. To test this hypothesis, we transiently overexpressed BMI1 or downregulated it using a transient transfection of a BMI1 shRNA vector in 293T (a derivative of HEK293) cells, and determined the expression of both miR-200c and miR-141 by qRT-PCR.…”

Section: Resultsmentioning

confidence: 99%

“…Because of its role in promoting oncogenic properties including CSC phenotype, inhibitors of BMI1 are of clinical importance. These inhibitors include miRNAs (miR-200c, miR-141 and miR-31), WNT inhibitors and certain pharmacological inhibitors [24–28], and a recently described cell permeable small molecule inhibitor PTC-209 [29]. PTC-209 represents a new class of inhibitors of gene expression that was identified using Gene Expression Modulation by Small Molecules (GEMS) technology designed to screen out small molecules that can inhibit BMI1 gene expression via interaction with its 5′ and 3′ untranslated regions (UTR) [29].…”

Section: Introductionmentioning

confidence: 99%

“…Recently, we showed that expression of the PcG proteins is inhibited by histone deacetylase inhibitors (HDACi) [24], and that HDACi may work through upregulation of miR-200c/141 cluster [27]. We also showed that inhibitors of polo-like kinase 1 (PLK1) can upregulate miR-200c/141 cluster, which indirectly results in downregulation of BMI1 and cancer stem cell phenotype [28]. In this study, we show that similar to miR-31 regulation by PcG proteins, BMI1 negatively regulates expression of miR-200c and miR-141, which targets BMI1 mRNA for degradation [27].…”

Section: Introductionmentioning

confidence: 99%

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A miR-200c/141-BMI1 autoregulatory loop regulates oncogenic activity of BMI1 in cancer cells

2016

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MicroRNAs (miRNAs) are known to function as oncomiRs or tumor suppressors and are important noncoding RNA regulators of oncogenesis. The miR-200c/141 locus on chromosome 12 encodes miR-200c and miR-141, two members of the miR-200 family, which have been shown to function as tumor suppressive miRNAs by targeting multiple oncogenic factors such as polycomb group protein BMI1. Here, we show that BMI1 reciprocally functions as a transcriptional repressor of the miR-200c/141 cluster and that BMI1 inhibitors upregulate expression of miR-200c and miR-141. Our data suggest that BMI1 binds to the miR-200c/141 promoter and regulates it through transcription factor binding motifs E-box 2 and Z-box 1 to repress expression of miR-200c/141 cluster. 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. Furthermore, inhibition of expression of miR-200c or miR-141 overcomes tumor suppressive effects of PTC-209 including induction of cellular senescence and downregulation of breast cancer stem cell phenotype. Therefore, our studies suggest a reciprocal regulation between BMI1 and miR-200c/141 cluster, and that BMI1 inhibitory drugs can further amplify their inhibitory effects on BMI1 via multiple mechanisms including posttranscriptional regulation by upregulating BMI1 targeting miRNAs.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A miR-200c/141-BMI1 autoregulatory loop regulates oncogenic activity of BMI1 in cancer cells

2016

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“…Along these lines, we have shown that miR-141 and miR200c are important senescence-regulatory miRNAs (32). Interestingly, these miRNAs are also induced by various pharmacological agents that induce senescence such as HDACi and BI 2536, a PLK1 inhibitor (32,53). As miR-31 is described as a tumor suppressive miRNA in breast and prostate cancers, and is induced by HDACi, we focused our studies in defining its regulation by HDACi and the potential novel role of miR-31 in cellular senescence.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-31 Is a Transcriptional Target of Histone Deacetylase Inhibitors and a Regulator of Cellular Senescence

Cho

Dimri

2015

Journal of Biological Chemistry

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Background: Histone deacetylase inhibitor (HDACi) inhibits expression of polycomb group proteins and can differentially regulate expression of miRNAs. Results: HDACi up-regulated expression of miR-31, which down-regulated BMI1 and induced cellular senescence. Conclusion: miR-31 is a novel target of HDACi, and is a novel regulator of cellular senescence. Significance: HDACi can be used to induce miR-31, which in turn can cause senescence in cancer cells.

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Human small intestine cancer cell membrane‐camouflaged quercetin‐melanin for antibacterial and antitumor activity

et al. 2021

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E. coli has become an important factor that can lead to cancer because of its ability to cause diverse intestinal changes. Nano‐polymer materials provide ideal drug delivery systems for preparing antibacterial and anti‐cancer drugs because of their unique structure, easy modification, and high drug loading. The modified natural melanin has the potential to be an excellent nano‐carrier. By improving the water‐solubility and biocompatibility of the loaded natural drug quercetin, the antibacterial effect of quercetin can be fully played. Here, natural melanin was extracted from frozen squid to synthesize carrier polydopamine (PDA) nanoparticles, and the natural drug quercetin (Q) was modified on the surface of PDA by π‐π bond and covalent bond action to produce melanin‐quercetin (PDA‐Q). We also developed human small intestinal cancer cells (HIC) membrane‐camouflaged melanin‐Quercetin (PDA‐Q) nanoparticles as an anti‐cancer platform in vivo. The potential bacteriostatic mechanism was likely driven by the penetration of PDA‐Q in E. coli cells, damaging the integrity of the membranes of E. coli and inducing cell death. The mice wound experiment and bacteremia model experiment revealed that C@PDA‐Q had a strong inhibitory effect on E. coli in vivo. In addition, the results of the in vitro tumor test also revealed that C@PDA‐Q had strong anti‐tumor activity against HIC cells of human small intestinal cancer, and the IC50 value was 12.3 ± 0.7 μg/ml, which was slightly better than that for cisplatin. As both melanin nanoparticles and HIC membrane are natural biomaterials, the synthesized C@PDA‐Q nano‐polymer material shows great potential for use in anti‐cancer nano‐drug loading.

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PLK1 Inhibition Down-regulates Polycomb Group Protein BMI1 via Modulation of the miR-200c/141 Cluster

Cited by 21 publications

References 51 publications

A miR-200c/141-BMI1 autoregulatory loop regulates oncogenic activity of BMI1 in cancer cells

A miR-200c/141-BMI1 autoregulatory loop regulates oncogenic activity of BMI1 in cancer cells

MicroRNA-31 Is a Transcriptional Target of Histone Deacetylase Inhibitors and a Regulator of Cellular Senescence

Human small intestine cancer cell membrane‐camouflaged quercetin‐melanin for antibacterial and antitumor activity

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