MicroRNA-101 Suppresses Tumor Cell Proliferation by Acting as an Endogenous Proteasome Inhibitor via Targeting the Proteasome Assembly Factor POMP

Zhang, Xin; Schulz, Ramona; Edmunds, Shelley J.; Krüger, Elke; Markert, Elke; Gaedcke, Jochen; Cormet‐Boyaka, Estelle; Ghadimi, Michael; Beißbarth, Tim; Levine, Arnold J.; Moll, Ute M.; Dobbelstein, Matthias

doi:10.1016/j.molcel.2015.05.036

Cited by 70 publications

(50 citation statements)

References 50 publications

(62 reference statements)

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“…S9A). Dis3 is potentially involved in Ig class switch recombination via targeting AID (25), whereas Pomp might be involved in plasma cell differentiation (26). Furthermore, we identified Arf4, Creld2, and Zfp36 among the genes enhancing or blocking plasma cell differentiation ( Fig.…”

Section: Identification Of Genes Important For B-cell Activation and mentioning

confidence: 79%

Efficient CRISPR-mediated mutagenesis in primary immune cells using CrispRGold and a C57BL/6 Cas9 transgenic mouse line

Chu

Graf

Wirtz

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

116

124

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International audienceApplying clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated protein 9 (Cas9)-mediated mutagenesis to primary mouse immune cells, we used high-fidelity single guide RNAs (sgRNAs) designed with an sgRNA design tool (CrispRGold) to target genes in primary B cells, T cells, and macrophages isolated from a Cas9 transgenic mouse line. Using this system, we achieved an average knockout efficiency of 80% in B cells. On this basis, we established a robust small-scale CRISPR-mediated screen in these cells and identified genes essential for B-cell activation and plasma cell differentiation. This screening system does not require deep sequencing and may serve as a precedent for the application of CRISPR/Cas9 to primary mouse cells

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Section: Identification Of Genes Important For B-cell Activation and mentioning

confidence: 79%

Efficient CRISPR-mediated mutagenesis in primary immune cells using CrispRGold and a C57BL/6 Cas9 transgenic mouse line

Chu

Graf

Wirtz

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

116

124

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“…11–13, 36, 37 To investigate the potential targets of microRNA-101, we utilized freely available web-based micoRNA target prediction resources; TargetScan, 38 miRanda 39 and Diana-microT. 40 We identified miR-101 that could potentially target SUB1.…”

Section: Resultsmentioning

confidence: 99%

“…The binding site for miR-101 at 3′-UTR of SUB1 is indicated (Figure 1a). MiR-101 is known to play tumor suppressor function by targeting several oncogenes including EZH2, 11 proteasome assembly factor POMP, 13 Cyclooxygenase-2 (COX2), 12 and others, we sought to determine its role in SUB1 regulation. We treated prostate cancer cell line DU145 with precursor miRNA, miR-101 and tested some of the potential targets.…”

Section: Resultsmentioning

confidence: 99%

MicroRNA-101 regulated transcriptional modulator SUB1 plays a role in prostate cancer

et al. 2016

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MicroRNA-101, a tumor suppressor microRNA is often down-regulated in cancer and is known to target multiple oncogenes. Some of the genes that are negatively regulated by miR-101 expression include histone methyltransferase EZH2, COX2, POMP, CERS6, STMN1, MCL-1 and ROCK2, among others. In the present study, we show that mir-101 targets transcriptional coactivator SUB1 homolog (Saccharomyces cerevisiae)/PC4 (positive cofactor 4) and regulates its expression. SUB1 is known to play diverse role in vital cell processes such as DNA replication, repair and heterochromatinization. SUB1 is known to modulate transcription and acts as a mediator between the upstream activators and general transcription machinery. Expression profiling in several cancers revealed SUB1 overexpression, suggesting a potential role in tumorigenesis. However, detailed regulation and function of SUB1 has not been elucidated. In this study, we show elevated expression of SUB1 in aggressive prostate cancer. Knockdown of SUB1 in prostate cancer cells resulted in reduced cell proliferation, invasion and migration in vitro, and tumor growth and metastasis in vivo. Gene expression analyses coupled with chromatin immunoprecipitation revealed that SUB1 binds to the promoter regions of several oncogenes such as polo-like kinase PLK1, C-MYC, serine threonine kinase BUB1B and regulates their expression. Additionally, we observed SUB1 down-regulated CDKN1B expression. PLK1 knockdown or use of PLK1 inhibitor can mitigate oncogenic function of SUB1 in benign prostate cancer cells. Thus, our study suggests that miR-101 loss results in increased SUB1 expression and subsequent activation of known oncogenes driving prostate cancer progression and metastasis. This study therefore demonstrates functional role of SUB1 in the prostate cancer and identifies its regulation, and potential downstream therapeutic targets of SUB1 in prostate cancer.

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“…Previously, several studies revealed that miR-124 results in a decrease in the proliferation ability of CRC cells by targeting ribose-phosphate pyrophosphokinase 1 and ribose 5-phosphate isomerase mRNAs (12), that miR-146a directs the symmetric division of colorectal cancer stem cells (13) and that miR-101 serves as an endogenous proteasome inhibitor that suppresses tumor cell proliferation via targeting of the proteasome assembly factor proteasome maturation protein (14). Therefore, attention has been focused on the activities of miRNA in cancer development.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-552 promotes tumor cell proliferation and migration by directly targeting DACH1 via the Wnt/β-catenin signaling pathway in colorectal cancer

et al. 2017

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Abstract. The purpose of the present study was to analyze the crucial role of microRNAs (miRNAs/miRs) involved in the proliferation and migration of colorectal cancer (CRC) and to investigate their underlying mechanisms. The present study discusses the expression and function of miR-552 in CRC. The expression level of miR-552 in CRC cells and tissues was observed, and it was suggested that the high expression of miR-552 accelerated the proliferation and migration of CRC cells in vitro. Notably, a result of the present study was that the cell fate determination factor Dachshund family transcription factor 1 (DACH1) was identified as a direct target of miR-552. Suppressing miR-552 expression in CRC cells increased endogenous DACH1 mRNA and protein levels, which was negatively correlated with miR-552. DACH1 performs an important role in the development of a number of neoplasms, and has the ability to regulate the Wnt/β-catenin signaling pathway as a novel predictive and diagnostic biomarker. Accordingly, it was concluded that miR-552 exerted a tumor-promoting role in CRC development by targeting DACH1, which may contribute to the increase in the rates of CRC proliferation and migration. miR-552 may serve as a potential diagnostic and prognostic biomarker for CRC. IntroductionColorectal cancer (CRC) has one of the highest cure rates of all types of malignant tumors (1), however remains ranked as the fourth leading cause of cancer-associated mortality in the world (2). In previous years, the morbidity and mortality rates of CRC have significantly increased due to an ageing population, and with changes in eating habits and lifestyles (3). The development of distant metastasis is a major cause of cancer-associated mortalities in CRC patients (4). Overwhelming evidence has demonstrated that aberrant expression of microRNA (miRNA/miR) contributes to CRC development by affecting the expression of the genes that regulate cancer progression (5).miRNAs, endogenous small non-coding regulatory RNAs measuring 18-25 nucleotides long (6), usually regulate gene expression in a number of tumor-associated signaling pathways at the post-transcriptional level, including the Wnt/β-catenin signaling pathway (7). As miRNAs tend to be localized to fragile chromosomal regions (8), they have the ability to adjust the levels of their corresponding mRNAs, and serve critical roles in the physiological and pathological processes of tumor development, which are a novel aspect of cancer studies. Previous evidence has demonstrated that miRNAs are involved in a number of biological processes, including proliferation, differentiation, migration, angiogenesis and protein splitting (9-11). miRNAs also serve as tumor promoter genes or tumor suppressor genes by negatively regulating their targets. These data suggest a possibility that miRNA is a novel focus for examining the current diagnosis and treatment of tumors.Previously, several studies revealed that miR-124 results in a decrease in the proliferation ability of CRC cells by targeting ribose-phosp...

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MicroRNA-101 Suppresses Tumor Cell Proliferation by Acting as an Endogenous Proteasome Inhibitor via Targeting the Proteasome Assembly Factor POMP

Cited by 70 publications

References 50 publications

Efficient CRISPR-mediated mutagenesis in primary immune cells using CrispRGold and a C57BL/6 Cas9 transgenic mouse line

Efficient CRISPR-mediated mutagenesis in primary immune cells using CrispRGold and a C57BL/6 Cas9 transgenic mouse line

MicroRNA-101 regulated transcriptional modulator SUB1 plays a role in prostate cancer

MicroRNA-552 promotes tumor cell proliferation and migration by directly targeting DACH1 via the Wnt/β-catenin signaling pathway in colorectal cancer

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