MicroRNA-143 Targets Syndecan-1 to Repress Cell Growth in Melanoma

Li, Ruiya; Zhang, Lingli; Jia, Lizhou; Duan, Yan; Li, Yan; Wang, Jie; Sha, Na

doi:10.1371/journal.pone.0094855

Cited by 38 publications

(42 citation statements)

References 31 publications

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“…Among these dysregulated miRNAs was miR-143 which was downregulated 4.8-fold in the arsenic-transformed prostate SCs, As-CSCs (Ngalame et al 2014b). The downregulation of miR-143 in As-CSCs is consistent with decreased expression of the miRNA in other prostate cancers (Ahmad et al 2013; Clape et al 2009; Xu et al 2011) and other cancer types including cervical (Lipeng et al 2012), lung (Ni et al 2013), gastric (Takagi et al 2009), leukemia (Akao et al 2009; Shen et al 2014), pancreatic (Pramanik et al 2011), melanoma (Li et al 2014), colorectal (Zhang et al 2012), osteosarcoma (Osaki et al 2011), and bladder (Noguchi et al 2011). In some of the above-mentioned studies, miR-143 was shown to act as a tumor suppressor, as restoration of miR143 in these cancer cells significantly reduced cancer cell properties.…”

Section: Introductionsupporting

confidence: 66%

Mitigation of arsenic-induced acquired cancer phenotype in prostate cancer stem cells by miR-143 restoration

Ngalame

Makia

Waalkes

et al. 2016

Toxicology and Applied Pharmacology

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Inorganic arsenic, an environmental contaminant and a human carcinogen is associated with prostate cancer. Emerging evidence suggests cancer stem cells (CSCs) are the driving force of carcinogenesis. Chronic arsenic exposure malignantly transforms the human normal prostate stem/progenitor cell (SC) line, WPE-stem to arsenic-cancer SCs (As-CSCs), through unknown mechanisms. MicroRNAs (miRNAs) are small, non-coding RNAs that negatively regulate gene expression at the posttranscriptional level. In prior work, miR-143 was markedly downregulated in As-CSCs, suggesting a role in arsenic-induced malignant transformation. In the present study, we investigated whether loss of miR-143 expression is important in arsenic-induced transformation of prostate SCs. Restoration of miR-143 in As-CSCs was achieved by lentivirus-mediated miR-143 overexpression. Cells were assessed bi-weekly for up to 30 weeks to examine mitigation of cancer phenotype. Secreted matrix metalloproteinase (MMP) activity was increased by arsenic-induced malignant transformation, but miR-143 restoration decreased secreted MMP-2 and MMP-9 enzyme activities compared with scramble controls. Increased cell proliferation and apoptotic resistance, two hallmarks of cancer, were decreased upon miR-143 restoration. Increased apoptosis was associated with decreased BCL2 and BCL-XL expression. miR-143 restoration dysregulated the expression of SC/CSC self-renewal genes including NOTCH-1, BMI-1, OCT4 and ABCG2. The anticancer effects of miR-143 overexpression appeared to be mediated by targeting and inhibiting LIMK1 protein, and the phosphorylation of cofilin, a LIMK1 substrate. These findings clearly show that miR-143 restoration mitigated multiple cancer characteristics in the As-CSCs, suggesting a potential role in arsenic-induced transformation of prostate SCs. Thus, miR-143 is a potential biomarker and therapeutic target for arsenic-induced prostate cancer.

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Section: Introductionsupporting

confidence: 66%

Mitigation of arsenic-induced acquired cancer phenotype in prostate cancer stem cells by miR-143 restoration

Ngalame

Makia

Waalkes

et al. 2016

Toxicology and Applied Pharmacology

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“…Although these downstream targets of miR-143 have been described in other cell lines [11,12], regulation of these proteoglycans by miR-143 in the glomerulus has not been reported previously.…”

Section: Discussionmentioning

confidence: 79%

“…Usually one miR has several targets. MiRs have been reported to regulate the proteoglycans in melanoma and smooth muscle cells [11,12]. Moreover, it has been shown that miRs play a significant role in glomerular diseases [13,14].…”

Section: Introductionmentioning

confidence: 99%

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Overexpression of TGF-β Inducible microRNA-143 in Zebrafish Leads to Impairment of the Glomerular Filtration Barrier by Targeting Proteoglycans

Müller-Deile

Gellrich

Schenk

et al. 2016

Cell Physiol Biochem

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Background: TGF-β is known as an important stress factor of podocytes in glomerular diseases. Apart from activation of direct pro-apoptotic pathways we wanted to analyze micro-RNA (miRs) driven regulation of components involved in the integrity of the glomerular filtration barrier induced by TGF-β. Since miR-143-3p (miR-143) is described as a TGF-β inducible miR in other cell types, we examined this specific miR and its ability to induce glomerular pathology. Methods: We analyzed miR-143 expression in cultured human podocytes after stimulation with TGF-β. We also microinjected zebrafish eggs with a miR-143 mimic or with morpholinos specific for its targets syndecan and versican and compared phenotype and proteinuria development. Results: We detected a time dependent, TGF-β inducible expression of miR-143 in human podocytes. Targets of miR-143 relevant in glomerular biology are syndecans and versican, which are known components of the glycocalyx. We found that syndecan 1 and 4 were predominantly expressed in podocytes while syndecan 3 was largely expressed in glomerular endothelial cells. Versican could be detected in both cell types. After injection of a miR-143 mimic in zebrafish larvae, syndecan 3, 4 and versican were significantly downregulated. Moreover, miR-143 overexpression or versican knockdown by morpholino caused loss of plasma proteins, edema, podocyte effacement and endothelial damage. In contrast, knockdown of syndecan 3 and syndecan 4 had no effects on glomerular filtration barrier. Conclusion: Expression of versican and syndecan isoforms is indispensable for proper barrier function. Podocyte-derived miR-143 is a mediator for paracrine and autocrine cross talk between podocytes and glomerular endothelial cells and can alter expression of glomerular glycocalyx proteins.

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“…Some cell type-specific regulations were consistent with previous findings. For example, miR-143-3p and miR-378a-3p are known to be regulated by TGF-β in non-renal cells [25,26]. Both miRs were also upregulated in cultured human podocytes after stimulation with TGF-β in our miR-screening.…”

Section: Discussionmentioning

confidence: 72%

Identification of Cell-and Disease-Specific Micro RNAs in Glomerular Pathologies

Müller-Deile¹,

Dannenberg²,

P³

et al. 2017

J Mol Genet Med

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Background: MicroRNAs (miRs) are small non-coding RNAs that regulate gene expression in physiological processes as well as in diseases. Currently miRs are already used to find novel mechanisms involved in diseases and in the future, they might serve as diagnostic markers. To identify miRs that play a role in glomerular diseases urinary miR-screenings are a frequently used tool. However, miRs that are detected in the urine might simply be filtered from the blood stream and could have been produced anywhere in the body, so they might be completely unrelated to the diseases. Methods:We performed a combined miR-screening in pooled urine samples from patients with different glomerular diseases as well as in cultured human podocytes, human mesangial cells, human glomerular endothelial cells, and human tubular cells. The miR-screening in renal cells was done in untreated conditions and after stimulation with TGF-β.Results: A merge of the detected regulated miRs led us to identify disease-specific, cell type-specific and cell stress-induced miRs. Further, urinary miRs from patients with different glomerular diseases could be assigned to the different renal cell types. Conclusion:Thus, a combined urinary and cell miR-screening can improve the interpretation of screening results. These data are useful to identify novel miRs potentially involved in glomerular diseases.

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MicroRNA-143 Targets Syndecan-1 to Repress Cell Growth in Melanoma

Cited by 38 publications

References 31 publications

Mitigation of arsenic-induced acquired cancer phenotype in prostate cancer stem cells by miR-143 restoration

Mitigation of arsenic-induced acquired cancer phenotype in prostate cancer stem cells by miR-143 restoration

Overexpression of TGF-β Inducible microRNA-143 in Zebrafish Leads to Impairment of the Glomerular Filtration Barrier by Targeting Proteoglycans

Identification of Cell-and Disease-Specific Micro RNAs in Glomerular Pathologies

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