Adenomatous polyposis coli (APC) regulates miR17-92 cluster through β-catenin pathway in colorectal cancer

Li, Yajuan; Lauriola, Mattia; Kim, Donghwa; Francesconi, Mirko; D’Uva, Gabriele; Shibata, Dave; Malafa, Mokenge P.; Yeatman, Timothy J.; Coppola, Domenico; Solmi, Rossella; Cheng, Jin Q.

doi:10.1038/onc.2015.522

Cited by 50 publications

(42 citation statements)

References 51 publications

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“…Ma and colleagues suggested that miR-17-5p promotes colorectal cancer development by targeting P130 (37). In addition, the expression level of miR-19a was significantly correlated with activated b-catenin in colorectal cancer and associated with the aggressive stage of tumor progression (38). In this study, we confirmed that the MIR17HG-miR-17-5p axis directly targeted BLNK, thus promoting the initiation and metastasis of colorectal cancer.…”

Section: Discussionsupporting

confidence: 79%

Long Noncoding RNA MIR17HG Promotes Colorectal Cancer Progression via miR-17-5p

et al. 2019

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Immune dysregulation plays a vital role in colorectal cancer initiation and progression. Long noncoding RNAs (lncRNA) exhibit multiple functions including regulation of gene expression. Here, we identified an immune-related lncRNA, MIR17HG, whose expression was gradually upregulated in adjacent, adenoma, and colorectal cancer tissue. MIR17HG promoted tumorigenesis and metastasis in colorectal cancer cells both in vitro and in vivo. Mechanistically, MIR17HG increased the expression of NF-kB/RELA by competitively sponging the microRNA miR-375. In addition, RELA transcriptionally activated MIR17HG in a positive feedback loop by directly binding to its promoter region. Moreover, miR-17-5p, one of the transcribed miRNAs from MIR17HG, reduced the expression of the tumor suppressor B-cell linker (BLNK), resulting in increased migration and invasion of colorectal cancer cells. MIR17HG also upregulated PD-L1, indicating its potential role in immunotherapy. Overall, these findings demonstrate that MIR17HG plays an oncogenic role in colorectal cancer and may serve as a promising therapeutic target. Significance: These findings provide mechanistic insight into the role of the lncRNA MIR17HG and its miRNA members in regulating colorectal cancer carcinogenesis and progression.

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Section: Discussionsupporting

confidence: 79%

Long Noncoding RNA MIR17HG Promotes Colorectal Cancer Progression via miR-17-5p

et al. 2019

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“…Early studies identified a correlation between increased expression of particular miRNAs and the proto-oncogene c-Myc [101]. More recent studies have shown that miRNAs can drive the transformation from adenoma to adenocarcinoma [102], and that the micro-RNA 17/92 cluster can regulate the expression of common CRC-associated genes, including BCL3 and PTEN [103,104]. Long ncRNAs, including HOTAIR, CCAT, MALAT-1, H19, and many others, have been associated with CRC development, invasion, and metastasis and with early diagnosis and prognosis [105].…”

Section: The Gut Microbiome and Non-coding Rnasmentioning

confidence: 99%

Impact of the gut microbiome on the genome and epigenome of colon epithelial cells: contributions to colorectal cancer development

2019

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In recent years, the number of studies investigating the impact of the gut microbiome in colorectal cancer (CRC) has risen sharply. As a result, we now know that various microbes (and microbial communities) are found more frequently in the stool and mucosa of individuals with CRC than healthy controls, including in the primary tumors themselves, and even in distant metastases. We also know that these microbes induce tumors in various mouse models, but we know little about how they impact colon epithelial cells (CECs) directly, or about how these interactions might lead to modifications at the genetic and epigenetic levels that trigger and propagate tumor growth. Rates of CRC are increasing in younger individuals, and CRC remains the second most frequent cause of cancer-related deaths globally. Hence, a more in-depth understanding of the role that gut microbes play in CRC is needed. Here, we review recent advances in understanding the impact of gut microbes on the genome and epigenome of CECs, as it relates to CRC. Overall, numerous studies in the past few years have definitively shown that gut microbes exert distinct impacts on DNA damage, DNA methylation, chromatin structure and non-coding RNA expression in CECs. Some of the genes and pathways that are altered by gut microbes relate to CRC development, particularly those involved in cell proliferation and WNT signaling. We need to implement more standardized analysis strategies, collate data from multiple studies, and utilize CRC mouse models to better assess these effects, understand their functional relevance, and leverage this information to improve patient care.

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“…A recent report demonstrated that a fecal microRNAs (miRNAs) can shape the composition of the gut microbiome [28], indicating a mechanism by which host cells can regulate the microbial community. In CRC, several miRNAs, such as miR-182, miR-503, and miR-17~92 cluster, can regulate multiple genes and pathways and have been found to promote malignant transformation and disease progression [29][30][31]. Interestingly, studies have also found that microbiome-derived metabolites can change host gene expression, including expression of miRNAs, in the colon [32,33].…”

Section: Introductionmentioning

confidence: 99%

Interaction Between Host MicroRNAs and the Gut Microbiota in Colorectal Cancer

Yuan

Burns

Subramanian

et al. 2017

Preprint

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BackgroundAlthough variation in gut microbiome composition has been linked with colorectal cancer (CRC), the factors that mediate the interactions between CRC tumors and the microbiome are poorly understood. MicroRNAs (miRNAs) are known to regulate CRC progression and patient survival outcomes. In addition, recent studies suggested that host miRNAs can also regulate bacterial growth and influence the composition of the gut microbiome. Here, we investigated the association between miRNAs expression in human CRC tumor and normal tissues and the microbiome composition associated with these same tissues.MethodWe sequenced the small RNAs from patient-matched tumor and normal tissue samples collected from 44 human CRC patients performed an integrated analysis with microbiome taxonomic composition data from these same samples. We then interrogated the functions of the bacteria correlated with miRNAs that were differentially expressed (DE) between tumor and matched normal tissues, as well as the functions of miRNAs correlated with bacterial taxa that have been previously associated with CRC, including Fusobacterium, Providencia, Bacteroides, Akkermansia, Roseburia, Porphyromonas, and Peptostreptococcus.ResultsWe identified 76 miRNAs as DE between CRC and normal tissue, including known oncogenic miRNAs miR-182, miR-503, and miR-17∼92. These DE miRNAs were correlated with the relative abundance of several bacterial taxa, including Firmicutes, Bacteroidetes, and Proteobacteria. Bacteria correlated with DE miRNAs were enriched with distinct predicted metabolic categories. Additionally, we found that miRNAs correlated with CRC-associated bacteria are predicted to regulate targets that are relevant for host-microbiome interactions, and highlight a possible role for miRNA-driven glycan production in the recruitment of pathogenic microbial taxa.ConclusionsOur work characterized a global relationship between microbial community composition and miRNA expression in human CRC tissues. Our results support a role for miRNAs in mediating a bi-directional host-microbiome interaction in CRC. In addition, we highlight sets of potentially interacting microbes and host miRNAs, suggesting several pathways that can be targeted via future therapies.

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Adenomatous polyposis coli (APC) regulates miR17-92 cluster through β-catenin pathway in colorectal cancer

Cited by 50 publications

References 51 publications

Long Noncoding RNA MIR17HG Promotes Colorectal Cancer Progression via miR-17-5p

Long Noncoding RNA MIR17HG Promotes Colorectal Cancer Progression via miR-17-5p

Impact of the gut microbiome on the genome and epigenome of colon epithelial cells: contributions to colorectal cancer development

Interaction Between Host MicroRNAs and the Gut Microbiota in Colorectal Cancer

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