Attenuation of the beta-catenin/TCF4 complex in colorectal cancer cells induces several growth-suppressive microRNAs that target cancer promoting genes

Schepeler, Troels; Holm, Anja; Halvey, Patrick J.; Nordentoft, Iver; Lamy, Philippe; Riising, Eva Madi; Christensen, Lise-Lotte; Thorsen, Kasper; Liebler, Daniel C.; Helin, Kristian; Ørntoft, Torben F.; Andersen, Claus Lindbjerg

doi:10.1038/onc.2011.453

Cited by 65 publications

(59 citation statements)

References 53 publications

(86 reference statements)

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“…The Wnt signaling pathway activation has been shown in several cancers and more specifically in breast cancer (Schlange et al 2007;Khalil et al 2012). Schepeler et al have shown that disruption of Wnt signaling leads to an increase in the levels of miR-139-5p, among other miRNAs, in colorectal carcinoma cells (Schepeler et al 2012). In our study, we observe components of the Wnt pathway being targets of miR-139-5p.…”

Section: Discussionsupporting

confidence: 62%

miR-139-5p is a regulator of metastatic pathways in breast cancer

Krishnan

Steptoe

Martin

et al. 2013

RNA

135

112

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Metastasis is a complex, multistep process involved in the progression of cancer from a localized primary tissue to distant sites, often characteristic of the more aggressive forms of this disease. Despite being studied in great detail in recent years, the mechanisms that govern this process remain poorly understood. In this study, we identify a novel role for miR-139-5p in the inhibition of breast cancer progression. We highlight its clinical relevance by reviewing miR-139-5p expression across a wide variety of breast cancer subtypes using in-house generated and online data sets to show that it is most frequently lost in invasive tumors. A biotin pull-down approach was then used to identify the mRNA targets of miR-139-5p in the breast cancer cell line MCF7. Functional enrichment analysis of the pulled-down targets showed significant enrichment of genes in pathways previously implicated in breast cancer metastasis (P < 0.05). Further bioinformatic analysis revealed a predicted disruption to the TGFβ, Wnt, Rho, and MAPK/PI3K signaling cascades, implying a potential role for miR-139-5p in regulating the ability of cells to invade and migrate. To corroborate this finding, using the MDA-MB-231 breast cancer cell line, we show that overexpression of miR-139-5p results in suppression of these cellular phenotypes. Furthermore, we validate the interaction between miR-139-5p and predicted targets involved in these pathways. Collectively, these results suggest a significant functional role for miR-139-5p in breast cancer cell motility and invasion and its potential to be used as a prognostic marker for the aggressive forms of breast cancer.

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Section: Discussionsupporting

confidence: 62%

miR-139-5p is a regulator of metastatic pathways in breast cancer

Krishnan

Steptoe

Martin

et al. 2013

RNA

135

112

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“…Over the past decade, the contribution of miRNAs (11), such as let-7 (12, 13), miR-17 (14,15), miR-21 (16)(17)(18)(19), miR-31 (20,21), miR-95 (22), miR-101 (23,24), miR-135 (25,26), miR-137 (27), miR-139 (28,29), miR-143 (30)(31)(32), miR-145 (31,33), miR-155 (34), miR-183 (35), and miR-195 (36), to colorectal carcinogenesis has been examined. In a previous study, we determined that miR-95 is frequently overexpressed in colorectal cancer and acts as an important inducer of proliferation via the negative regulation of SNX1 expression (22).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-202-3p Inhibits Cell Proliferation by Targeting ADP-Ribosylation Factor-like 5A in Human Colorectal Carcinoma

Wang

Huang

Guo

et al. 2014

Clinical Cancer Research

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Purpose: MicroRNAs (miRNA) that are strongly implicated in carcinogenesis have recently reshaped our understanding of the role of non-protein-coding RNAs. Here, we focused on the function and molecular mechanism of miR-202-3p and its potential clinical application in colorectal cancer.Experimental Design: miR-202-3p expression was determined by quantitative reverse transcriptase PCR (qRT-PCR) in 94 colorectal cancer tissues and corresponding noncancerous tissues (NCT). Cell proliferation and colony formation assays in vitro and xenograft experiments in vivo were used to evaluate the effect of miR-202-3p on colorectal cancer cell proliferation. Luciferase assay and Western blot analysis were performed to validate the potential targets of miR-202-3p after the preliminary screening by online prediction and microarray analysis. The mRNA and protein levels of target genes were detected by qRT-PCR and immunohistochemical staining. The copy number of pre-miR-202 was measured by quantitative PCR.Results: First, miR-202-3p was significantly downregulated in 46.7% colorectal cancer samples compared with NCTs. The overexpression of miR-202-3p inhibited colorectal cancer cell growth in vitro and repressed tumorigenesis in nude mice. Then, miR-202-3p downregulated ADP-ribosylation factor-like 5A (ARL5A) protein level by binding to its 3 0 untranslated region, and knockdown of ARL5A phenocopied the proliferation inhibition effect of miR-202-3p. Furthermore, both of ARL5A mRNA and protein levels were upregulated in colorectal cancer samples compared with NCTs and high ARL5A protein levels predicted a poor prognosis. Conclusions: miR-202-3p might function as a tumor suppressor in colorectal cancer, and ARL5A, the functional target of miR-202-3p in colorectal cancer, is a potential prognostic factor for colorectal cancer. Clin Cancer Res; 20(5); 1146-57. Ó2013 AACR.

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“…Some miRNAs are related to tumors of the digestive system: miRNA 27a [hepatocarcinoma (24)], miRNA 30e-3p [colorectal cancer (25)], miRNA 107 [gastric cancer (26)], miRNA 379 [hepatocarcinoma (27)]. …”

Section: Resultsmentioning

confidence: 99%

Tongue Cancer and Epigenetic Factors: An in-vitro Study on 298 Micro-RNAS

et al. 2012

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Oral Squamous Cell Carcinoma (OSCC) is the sixth most frequent malignant tumour. There is some evidence that tongue cancer has a higher local failure rate and poorer prognosis than other anatomical sites in the oral cavity. We used tongue squamous cell carcinoma cell lines harbouring mutated p53/ p16 as tongue cancer models to study the influences exerted by p53 and p16 genes on the expression of micro RNAs (miRNAs). The study was performed on microarray chips harbouring 298 miRNA sequences. OSCC cell lines used in this study were SCC-4, SCC-15 and SCC-25, all three carrying mutated/hypermethylated p53/pI6. The expression values normalized to healthy control of298 miRNAs were obtained for each cell line. MiRNA 196b was found hyperexpressed in the three cell lines. MiRNAs 19b-l, 21, 27a, 30d, 134, 339, 379 and 465 were found altered in two out of three cell lines. miRNAs found altered in one cell line out of three were: 7b, 23a, 25, 30c, 30e-3p, 107, 125b, 124a, 214, 216, 325 and 384. A literature review for each miRNA found significant was undertaken. Some miRNAs have a well-known role in oral cancer, some have been put in correlation with other cancers/diseases, others are found significant for the first time. These early results in tongue cancer cell lines harbouring mutation of p16/p53 need further analyses to understand whether this variation of miRNA levels are directly influenced by the malfunction of these proteins or if, vice-versa, altered miRNA levels influence the function of p16 and p53.

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Attenuation of the beta-catenin/TCF4 complex in colorectal cancer cells induces several growth-suppressive microRNAs that target cancer promoting genes

Cited by 65 publications

References 53 publications

miR-139-5p is a regulator of metastatic pathways in breast cancer

miR-139-5p is a regulator of metastatic pathways in breast cancer

MicroRNA-202-3p Inhibits Cell Proliferation by Targeting ADP-Ribosylation Factor-like 5A in Human Colorectal Carcinoma

Tongue Cancer and Epigenetic Factors: An in-vitro Study on 298 Micro-RNAS

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