The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2

Park, Sun Mi; Gaur, Arti; Lengyel, Ernst; Marynen, Peter

doi:10.1101/gad.1640608

Cited by 2,060 publications

(2,081 citation statements)

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“…A recent study demonstrated that the miRNA-200 family (miR-141, miR-200a, b, c, and miR-429) and miR-192/215 inhibit E-cadherin expression by targeting ZEB1 and ZEB2. [33][34][35][36][37] These previous reports suggest that solid-pseudopapillary neoplasm-specific downregulation of the miR-200 family and miR-192/215 targets components of the Wnt/b-catenin, Hedgehog, androgen receptor signaling pathways as well as genes associated with epithelial-mesenchymal transition. These effects ultimately result in decreased expression of epithelial markers.…”

Section: Discussionmentioning

confidence: 84%

Characterization of gene expression and activated signaling pathways in solid-pseudopapillary neoplasm of pancreas

et al. 2014

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Solid-pseudopapillary neoplasm is an uncommon pancreatic tumor with distinct clinicopathologic features. Solid-pseudopapillary neoplasms are characterized by mutations in exon 3 of CTNNB1. However, little is known about the gene and microRNA expression profiles of solid-pseudopapillary neoplasms. Thus, we sought to characterize solid-pseudopapillary neoplasm-specific gene expression and identify the signaling pathways activated in these tumors. Comparisons of gene expression in solid-pseudopapillary neoplasm to pancreatic ductal carcinomas, neuroendocrine tumors, and non-neoplastic pancreatic tissues identified solid-pseudopapillary neoplasm-specific mRNA and microRNA profiles. By analyzing 1686 (1119 upregulated and 567 downregulated) genes differentially expressed in solid-pseudopapillary neoplasm, we found that the Wnt/b-catenin, Hedgehog, and androgen receptor signaling pathways, as well as genes involved in epithelial mesenchymal transition, are activated in solid-pseudopapillary neoplasms. We validated these results experimentally by assessing the expression of b-catenin, WIF-1, GLI2, androgen receptor, and epithelial-mesenchymal transitionrelated markers with western blotting and immunohistochemistry. Our analysis also revealed 17 microRNAs, especially the miR-200 family and miR-192/215, closely associated with the upregulated genes associated with the three pathways activated in solid-pseudopapillary neoplasm and epithelial mesenchymal transition. Our results provide insight into the molecular mechanisms underlying solid-pseudopapillary neoplasm tumorigenesis and its characteristic less epithelial cell differentiation than the other common pancreatic tumors.

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Section: Discussionmentioning

confidence: 84%

Characterization of gene expression and activated signaling pathways in solid-pseudopapillary neoplasm of pancreas

et al. 2014

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“…miR-141 and miR-200a belong to the evolutionarily conserved miR-200 family. 17 The miR-200 family has been shown to determine the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2, 25 and a clinical study reveals that serum levels of miR-141 can be used as a biomaker of prostate cancer. 26 Abundant expression of miR-200a has been also shown in some prostate cancer cell lines.…”

Section: Discussionmentioning

confidence: 99%

miR-148a is an androgen-responsive microRNA that promotes LNCaP prostate cell growth by repressing its target CAND1 expression

Murata

Takayama

Katayama

et al. 2010

Prostate Cancer Prostatic Dis

131

105

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Recent advances in cancer biology reveal that microRNAs (miRNAs) are involved in the regulation of cancer-related genes, or they function as tumor suppressors or oncogenes. In prostate cancer, evidence has accumulated for the contribution of the androgen-dependent gene network to tumor growth, although the precise functions of miRNAs in prostate cancer remain to be investigated. Here, we identified androgen-responsive miRNAs by the short RNA sequencing analysis in LNCaP prostate cancer cells. Among 10 miRNAs with known sequences, we have determined that miR148a reduces the expression of cullin-associated and neddylation-dissociated 1 (CAND1), a negative regulator of SKP1-Cullin1-F-box (SCF) ubiquitin ligases, by binding to the 3 0 -untranslated region of CAND1 mRNA. CAND1 knockdown by small interfering RNA promoted the proliferation of LNCaP cells. Our study indicates the potential contribution of miR-148a to the growth of human prostate cancer.

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“…[8][9][10][11][12] Most studies of molecular diagnosis of tissue of origin used messenger RNA (mRNA) profiling of tumor samples. 8,[13][14][15] MicroRNAs, 21-23-nucleotide-long functional RNAs, have an important function in tissue differentiation 16,17 and tumorigenesis, 18,19 and have highly tissue-specific expression patterns. [20][21][22] The unique expression profiles of microRNAs characteristic of each tissue and the malignancies arising in them can permit their accurate identification.…”

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confidence: 99%

Validation of a microRNA-based qRT-PCR test for accurate identification of tumor tissue origin

et al. 2010

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Identification of the tissue of origin of a tumor is vital to its management. Previous studies showed tissuespecific expression patterns of microRNA and suggested that microRNA profiling would be useful in addressing this diagnostic challenge. MicroRNAs are well preserved in formalin-fixed, paraffin-embedded (FFPE) samples, further supporting this approach. To develop a standardized assay for identification of the tissue origin of FFPE tumor samples, we used microarray data from 504 tumor samples to select a shortlist of 104 microRNA biomarker candidates. These 104 microRNAs were profiled by proprietary quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) on 356 FFPE tumor samples. A total of 48 microRNAs were chosen from this list of candidates and used to train a classifier. We developed a clinical test for the identification of the tumor tissue of origin based on a standardized protocol and defined the classification criteria. The test measures expression levels of 48 microRNAs by qRT-PCR, and predicts the tissue of origin among 25 possible classes, corresponding to 17 distinct tissues and organs. The biologically motivated classifier combines the predictions generated by a binary decision tree and K-nearest neighbors (KNN). The classifier was validated on an independent, blinded set of 204 FFPE tumor samples, including nearly 100 metastatic tumor samples. The test predictions correctly identified the reference diagnosis in 85% of the cases. In 66% of the cases the two algorithm predictions (tree and KNN) agreed on a single-tissue origin, which was identical to the reference diagnosis in 90% of cases. Thus, a qRT-PCR test based on the expression profile of 48 tissue-specific microRNAs allows accurate identification of the tumor tissue of origin.

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The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2

Abstract: [Keywords: Ovarian cancer; tumor progression; EMT; NCI60] Supplemental material is available at http://www.genesdev.org.

Cited by 2,060 publications

References 46 publications

Characterization of gene expression and activated signaling pathways in solid-pseudopapillary neoplasm of pancreas

Characterization of gene expression and activated signaling pathways in solid-pseudopapillary neoplasm of pancreas

miR-148a is an androgen-responsive microRNA that promotes LNCaP prostate cell growth by repressing its target CAND1 expression

Validation of a microRNA-based qRT-PCR test for accurate identification of tumor tissue origin

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