miR-142-3p attenuates breast cancer stem cell characteristics and decreases radioresistance in vitro

Troschel, Fabian M.; Böhly, Nicolas; Borrmann, Katrin; Braun, Timo; Schwickert, Axel C.; Kiesel, L.; Eich, Hans Theodor; Götte, Martin; Greve, Burkhard

doi:10.1177/1010428318791887

Cited by 91 publications

(57 citation statements)

References 51 publications

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“…For reverse transcription, the High-Capacity cDNA Reverse Transcription Kit was used, and qPCR was then performed on a Rotor-Gene Q machine (Qiagen). All proceedings were handled according to the manufacturer's instructions and as previously described [7]. A list of the primers used can be found in Supplementary Table S2.…”

Section: Qpcrmentioning

confidence: 99%

“…CD44 and LIFR positivity were analyzed 48 h after transfection using CD44 APC (BD Pharmingen, Franklin Lakes, NJ, USA) or phycoerythrin (PE) conjugated mouse anti-human LIFR antibodies (R&D Systems, Minneapolis, MN, USA) and their corresponding isotype controls (APC isotype from BD Pharmingen, PE isotype from R&D Systems). All experiments were performed according to manufacturer's instructions and as previously described [7]. Catalogue numbers for the antibodies used are given in Supplementary Table S4.…”

Section: Flow Cytometrymentioning

confidence: 99%

“…Several overlapping but not identical markers have been identified to quantify BCSCs, including CD44, aldehyde dehydrogenase (ALDH) and multidrug resistance (MDR)-efflux systems [4,5]. Numerous studies have been published in search for pathways to downregulate BCSC characteristics [6,7].…”

Section: Introductionmentioning

confidence: 99%

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Knockdown of Musashi RNA Binding Proteins Decreases Radioresistance but Enhances Cell Motility and Invasion in Triple-Negative Breast Cancer

Troschel

Minte

Ismail

et al. 2020

IJMS

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The therapeutic potential of Musashi (MSI) RNA-binding proteins, important stemness-associated gene expression regulators, remains insufficiently understood in breast cancer. This study identifies the interplay between MSI protein expression, stem cell characteristics, radioresistance, cell invasiveness and migration. MSI-1, MSI-2 and Notch pathway elements were investigated via quantitative polymerase chain reaction (qPCR) in 19 triple-negative breast cancer samples. Measurements were repeated in MDA-MB-231 cells after MSI-1 and -2 siRNA-mediated double knockdown, with further experiments performed after MSI silencing. Flow cytometry helped quantify expression of CD44 and leukemia inhibitory factor receptor (LIFR), changes in apoptosis and cell cycle progression. Proliferation and irradiation-induced effects were assessed using colony formation assays. Radiation-related proteins were investigated via Western blots. Finally, cell invasion assays and digital holographic microscopy for cell migration were performed. MSI proteins showed strong correlations with Notch pathway elements. MSI knockdown resulted in reduction of stem cell marker expression, cell cycle progression and proliferation, while increasing apoptosis. Cells were radiosensitized as radioresistance-conferring proteins were downregulated. However, MSI-silencing-mediated LIFR downregulation resulted in enhanced cell invasion and migration. We conclude that, while MSI knockdown results in several therapeutically desirable consequences, enhanced invasion and migration need to be counteracted before knockdown advantages can be fully exploited.

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Section: Qpcrmentioning

confidence: 99%

Section: Flow Cytometrymentioning

confidence: 99%

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Knockdown of Musashi RNA Binding Proteins Decreases Radioresistance but Enhances Cell Motility and Invasion in Triple-Negative Breast Cancer

Troschel

Minte

Ismail

et al. 2020

IJMS

Self Cite

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“…Studies reported that miR-142-3p could arrest invasiveness of breast cancer cell via targeting different genes such as WASL, integrin alpha V, and additional cytoskeletal elements (Schwickert et al, 2015), while other reports showed that overexpression of miR-142-3p is probably related to metastasis in breast cancer (Pollari et al, 2012;Volinia et al, 2012). A recent study showed miR-142-3p could downregulate cancer stem cell characteristics and radioresistance by targeting β catenin in breast cancer (Troschel et al, 2018 In addition, miR-330, miR-145, and miR-34a were upregulated by the induction of miR-142-3p and Bach-1. CXCR4: C-X-C chemokine receptor type 4; miR: microRNA; MMP9: matrix metalloproteinase-9; VEGFR: vascular endothelial growth factor receptor [Color figure can be viewed at wileyonlinelibrary.com] expression ( Figure 7).…”

Section: The Mir-142-3p Mimic Sequence Could Increase the Level Ofmentioning

confidence: 99%

miR‐142‐3p as tumor suppressor miRNA in the regulation of tumorigenicity, invasion and migration of human breast cancer by targeting Bach‐1 expression

Mansoori

Mohammadi

Ghasabi

et al. 2018

Journal Cellular Physiology

110

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Background Breast cancer is the most common type of cancer among women, and despite improved treatments, it remains a major challenge. However, improved mechanistic insight may lead to novel therapeutic strategies. miR‐142‐3p belongs to the miR‐142 family and is involved in pathogenesis and metastasis of various types of malignancies by targeting several important messenger RNAs (mRNAs) including Bach‐1. This is especially true for breast cancer, where Bach‐1 is involved in the metastatic spread by deregulation of metastasis‐associated genes. Methods In this study, we collected 24 breast cancer tissues with 24 adjusted normal tissues to measure the expression levels of miR‐142‐3p and Bach‐1 mRNA using quantitative reverse‐transcription polymerase chain reaction (qRT‐PCR) and IHC. miR‐142‐3p targeting of Bach‐1 expression in MCF‐7 and MDA‐MB‐468 breast cancer cells was evaluated using bioinformatics, qRT‐PCR and western blot analyses. The cellular proliferation, invasion, and migration were assessed by MTT, transwell matrigel and wound healing assay and the EMT‐associated proteins C‐X‐C chemokine receptor type 4 (CXCR‐4), matrix metalloproteinase‐9 (MMP9), and vascular endothelial growth factor receptor (VEGFR) were analyzed by western blot analysis. Also, the expression levels of tumor suppressors including miR‐330, miR‐145, and miR‐34a were estimated by qRT‐PCR. Results Analysis of paired specimens of primary malignant and normal tissues showed that miR‐142‐3p was downregulated, while Bach‐1 mRNA and protein both were overexpressed in the breast cancer tumors. This inverse relationship was confirmed by cell line experiments demonstrating that miR‐142‐3p expression reduced Bach‐1 mRNA levels. Furthermore, replacement of miR‐142‐3p could inhibit the proliferation, invasion, and migration in breast cancer potentially by targeting of Bach‐1 mRNA and subsequent inhibition of CXCR4, MMP9, and VEGFR protein expressions. In addition, induction of miR‐142‐3p could upregulate tumor suppressor miRNAs, including miR‐330, miR‐145, and miR34a. Conclusion For the first time, our results revealed that miR‐142‐3p could target Bach‐1in breast cancer cells leading to the reduction of EMT‐related proteins and reduced cell proliferation, invasion, and migration. The results also demonstrated that miR‐142‐3p could regulate important tumor suppressor miRNAs in breast cancer cells. In conclusion, our results suggest that miR‐142‐3p could be a good candidate for the targeted therapy of breast cancer, especially for the invasive type.

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“…The question remains whether mutations in solid tumors, in which miR-142-3p acts predominantly as a tumor suppressor, among others targeting and downregulating TGFB1R and HMGB1 63,64 , may also have functional consequences. It was shown that miR-142-3p plays a role in different solid tumors (e.g., breast 65,66 , ovarian 67 , colorectal 68,69 , and lung cancer [70][71][72] ). Hsa-miR-142 constitutes an example showing that cancer-specific enrichment of mutations may be a strong indicator of their functional relevance for cancer.…”

Section: Hsa-mir-142mentioning

confidence: 99%

Pan-Cancer analysis of somatic mutations in miRNA genes

Urbanek-Trzeciak

Galka-Marciniak

Nawrocka

et al. 2020

Preprint

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175)miRNAs are considered important players in oncogenesis, serving either as oncomiRs or suppressormiRs. Although the accumulation of somatic alterations is an intrinsic aspect of cancer development and many important cancer-driving mutations have been identified in protein-coding genes, the area of functional somatic mutations in miRNA genes is heavily understudied. Here, based on analysis of the whole-exome sequencing of over 10,000 cancer/normal sample pairs deposited within the TCGA repository, we identified and characterized over 10,000 somatic mutations in miRNA genes and showed that some of the genes are overmutated in Pan-Cancer and/or specific cancers. Nonrandom occurrence of the identified mutations was confirmed by a strong association of overmutated miRNA genes with KEGG pathways, most of which were related to specific cancer types or cancer-related processes. Additionally, we showed that mutations in some of the overmutated genes correlate with miRNA expression, cancer staging, and patient survival. Our results may also be the first step (form the basis and provide the resources) in the development of computational and/or statistical approaches/tools dedicated to the identification of cancerdriver miRNA genes. The results published here are based upon data generated by the TCGA Research Network: https://www.cancer.gov/tcga. This work was supported by research grants from the Polish National Science Centre [2016/22/A/NZ2/00184 (to P.K.) and 2015/17/N/NZ3/03629 (to M.O.U-T.)] Authors contributions MUTparticipated in conceiving the study, wrote all the scripts, performed most of the computational and statistical analyses, drafted the manuscript, prepared figures, tables, and supplementary materials; PGMparticipated in conceiving the study, discussed the study on all steps of analyses, participated in manuscript preparation, performed some analyses (3D structures); PNdiscussed the analyses on all steps of the study, performed some analyses, participated in manuscript preparation; EKperformed the sequencing experiments, critically read and corrected manuscript; SSperformed the sequencing experiments, critically read and corrected manuscript; MGprovided samples for the hsa-miR-1324 and hsa-miR-142 sequencing validation experiments, advised on hematological neoplasms and head and neck cancer, critically read and corrected manuscript; PKreceived financing, participated in conceiving the study, supervised and coordinated the study, drafted the manuscript (with MUT).

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miR-142-3p attenuates breast cancer stem cell characteristics and decreases radioresistance in vitro

Cited by 91 publications

References 51 publications

Knockdown of Musashi RNA Binding Proteins Decreases Radioresistance but Enhances Cell Motility and Invasion in Triple-Negative Breast Cancer

Knockdown of Musashi RNA Binding Proteins Decreases Radioresistance but Enhances Cell Motility and Invasion in Triple-Negative Breast Cancer

miR‐142‐3p as tumor suppressor miRNA in the regulation of tumorigenicity, invasion and migration of human breast cancer by targeting Bach‐1 expression

Pan-Cancer analysis of somatic mutations in miRNA genes

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