miR-493 induction during carcinogenesis blocks metastatic settlement of colon cancer cells in liver

Okamoto, Koji; Ishiguro, Takehiko; Midorikawa, Yutaka; Ohata, Hirokazu; Izumiya, Masashi; Tsuchiya, Naoto; Sato, Ai; Sakai, Hiroaki; Nakagama, Hitoshi

doi:10.1038/emboj.2012.25

Cited by 66 publications

(78 citation statements)

References 43 publications

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“…miR-199a targeted the glycosylation enzyme ST6GAL1, reduced the sialylation of Necl-2, indirectly reduced the protein level of Necl-2, and enhanced ErbB2/ErbB3 signaling (32). It was reported that miR-493 inhibited the formation of metastatic foci and thus prevented liver metastasis of colon cancer cells (33). miR-493, was found to be reduced in lung cancer cells and tissues and to suppress cell invasion and proliferation by blocking E2F1 (34).…”

Section: Discussionmentioning

confidence: 99%

miR-493-5p attenuates the invasiveness and tumorigenicity in human breast cancer by targeting FUT4

et al. 2016

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Abstract. Breast cancer is a leading cause of cancer-related mortality among women. Altered fucosylation was found to be closely associated with tumorigenesis and metastasis of breast cancer. MicroRNAs (miRNAs) are important regulators of cell proliferation and metastasis, and aberrant miRNA expression has been observed in breast cancer. The present study aimed to evaluate the level of fucosyltransferase IV (FUT4) and miR-493-5p in breast cancer and investigate their relationship. In the present study, we demonstrated the differential expressional profiles of FUT4 and miR-493-5p in 29 clinical breast cancer tissues, matched adjacent tissue samples and two breast carcinoma cell lines (MCF-7 and MDA-MB-231). Briefly, altered expression levels of FUT4 modified the invasive activities and tumorigenicity of the MCF-7 and MDA-MB-231 cells. Further study demonstrated that miR-493-5p plays a role as a suppressor in breast cancer cell invasion and tumorigenicity. Moreover, the expression levels of miR-493-5p were inversely proportional to those of FUT4 both at the mRNA and protein levels. Luciferase reporter assays confirmed that miR-493-5p bound to the 3'-untranslated (3'-UTR) region of FUT4, and inhibited the expression of FUT4 in breast cancer cells. Taken together, our data suggest that FUT4 may have a potential role in the treatment of breast cancer, as well as miR-493-5p is a novel regulator of invasiveness and tumorigenicity of breast cancer cells through targeting FUT4. The miR-493-5p/FUT4 pathway has therapeutic potential in breast cancer. IntroductionBreast cancer is the most common invasive cancer and the second cause of cancer-related death in women (1,2). Each year more than a half a million new cases of breast cancer are diagnosed in the US and Europe (3), and in China. Breast cancer is a very heterogeneous disease. Some patients are cured by the surgical removal of the primary tumor while other patients suffer from metastasis and progression of the disease, despite adjuvant therapy. Therefore, it is essential to develop effective and safer therapeutic modalities against breast cancer.Glycosylation is one of the important steps of protein post-translational modifications, and ~50% of proteins are glycosylated (4). Protein glycosylation plays a role in a variety of cellular biological functions, such as cell-cell and cell-substrate adhesion, membrane organization, cell immunogenicity and protein targeting (5). Specific changes in the glycosylation patterns of cell surface glycoprotein have been shown to enhance the metastatic potential of tumor cells. Aberrant expression of fucosylated glycans has also been detected in various types of tumors.The fucosyltransferase (FUT) family is a group of fucosylation synthases that catalyze the transfer of L-fucose (Fuc) from an activated GDP-β-L-Fuc to various acceptor molecules such as N-acetyllactosamine. The transfer of Fuc residue from the donor substrate, GDP-Fuc, is catalyzed to the oligosaccharide acceptor in a1, a1, FUT4, FUT5, FUT6, FUT7, FUT9, FUT10 and FUT1...

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Section: Discussionmentioning

confidence: 99%

miR-493-5p attenuates the invasiveness and tumorigenicity in human breast cancer by targeting FUT4

et al. 2016

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“…Indeed, high levels of miR-493 and miR-493(*), but not pri-miR-493, in primary colon cancer were inversely related to the presence of liver metastasis, and attributed to an increase of miR-493 expression during carcinogenesis [112].…”

Section: Mirnas and Metastasismentioning

confidence: 99%

microRNA: New Players in Metastatic Process

Triulzi¹,

Iorio²,

Tagliabue³

et al. 2013

Oncogene and Cancer - From Bench to Clinic

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“…Microarray analyses were performed using Agilent Whole Human Genome 8 Â 60 K Oligo microarrays (24). Microarray data were accessible through Gene Expression Omnibus database (accession number GSE64999).…”

Section: Gene Set Enrichment Analysesmentioning

confidence: 99%

Establishment and Characterization of an In Vitro Model of Ovarian Cancer Stem-like Cells with an Enhanced Proliferative Capacity

Ishiguro

Sato²,

Ohata³

et al. 2016

Cancer Research

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The establishment of cancer stem-like cell (CSC) culture systems may be instrumental in devising strategies to fight refractory cancers. Inhibition of the Rho kinase ROCK has been shown to favorably affect CSC spheroid cultures. In this study, we show how ROCK inhibition in human serous ovarian cancer (SOC) cells can help establish a CSC system, which illuminates cancer pathophysiology and its treatment in this setting. In the presence of a ROCK kinase inhibitor, spheroid cultures of SOC cells expressed characteristic CSC markers including ALDH1A1, CD133, and SOX2, along with differentiation and tumorigenic capabilities in mouse xenograft models of human SOC. High expression levels of ALDH, but not CD133, correlated with spheroid formation CSC marker expression and tumor forming capability. In clinical specimens of SOC, high levels of ALDH1A1 correlated with advanced stage and poor prognosis. Pharmacologic or genetic blockade of ALDH blocked cell proliferation and reduced expression of SOX2, the genetic ablation of which abolished spheroid formation, whereas SOX2 overexpression inhibited ALDH1A1 expression and blocked spheroid proliferation. Taken together, our findings illustrated a new method to culture human ovarian CSC, and they defined a reciprocal regulatory relationship between ALDH1A1 and SOX2, which impacts ovarian CSC proliferation and malignant progression. Cancer Res; 76(1); 150-60. Ó2015 AACR.

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miR-493 induction during carcinogenesis blocks metastatic settlement of colon cancer cells in liver

Cited by 66 publications

References 43 publications

miR-493-5p attenuates the invasiveness and tumorigenicity in human breast cancer by targeting FUT4

miR-493-5p attenuates the invasiveness and tumorigenicity in human breast cancer by targeting FUT4

microRNA: New Players in Metastatic Process

Establishment and Characterization of an In Vitro Model of Ovarian Cancer Stem-like Cells with an Enhanced Proliferative Capacity

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