Induction of Epithelial-Mesenchymal Transition and Down-Regulation of miR-200c and miR-141 in Oxaliplatin-Resistant Colorectal Cancer Cells

Tanaka, Shota; Hosokawa, Mika; Yonezawa, Takeshi; Hayashi, Wataru; Iwakawa, Seigo

doi:10.1248/bpb.b14-00695

Cited by 61 publications

(48 citation statements)

References 34 publications

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“…However, we previously reported that the invasion activity of SW620/OxR cells was higher than that of SW620 cells, 11) as also observed in the present study. These results suggest that the acquisition of L-OHP resistance may inhibit the incorporation of let-7a, let-7b, and let-7g into exosomes.…”

Section: Discussionsupporting

confidence: 88%

“…Cell Culture The human CRC cell lines SW480 (DS Pharmabiomedical, Osaka, Japan), SW620 (American Tissue Culture Collection, Manassas, VA, U.S.A.), and SW620/OxR developed from SW620 cells as previously reported 11) were maintained in Leibovitz 15 medium (Life Technologies Corp., Carlsbad, CA, U.S.A.) supplemented with 10% fetal bovine serum (Sigma-Aldrich, St. Louis, MO, U.S.A.), 100 U/mL penicillin, and 100 µg/mL streptomycin at 37°C with 100% air. SW620/OxR cells were maintained in the presence of 80 µM L-OHP and were cultured without L-OHP for 1 passage before experiments.…”

Section: Methodsmentioning

confidence: 99%

“…10) We previously demonstrated that the invasion activity of SW620/OxR cells was higher than that of SW620 cells. 11) In the present study, we examined the effects of Zeb on invasion activities and the intracellular and exosomal expression levels of let-7 family members in these three CRC cell lines.…”

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confidence: 99%

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Effects of Zebularine on Invasion Activity and Intracellular Expression Level of let-7b in Colorectal Cancer Cells

Tanaka

Hosokawa

Matsumura

et al. 2017

Biological & Pharmaceutical Bulletin

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The effects of zebularine, a DNA methyltransferase inhibitor, on the invasion activity as well as intracellular expression level of let-7b, tumor suppressor microRNA, were examined in three human colorectal cancer (CRC) cell lines: SW480, SW620, and oxaliplatin-resistant SW620 (SW620/OxR). Zebularine suppressed the invasion activity of SW620 and SW620/OxR cells. The intracellular expression level of let-7b was upregulated by zebularine in SW620 and SW620/OxR cells. The overexpression of let-7b by the transfection of let-7b mimic suppressed invasion activity in SW620 and SW620/OxR cells. These results suggest that zebularine may inhibit invasion activity by up-regulating the intracellular expression level of let-7b in high-invasive CRC cells.Key words invasion; zebularine; let-7b; oxaliplatin-resistant; colorectal cancer DNA methylation is a major epigenetic mechanism of gene expression level. Zebularine (Zeb) has been shown to inhibit DNA methyltransferase (DNMT). Furthermore, Zeb and other DNMT inhibitors, such as decitabine (DAC) and azacitidine (AC), exert differential effects on gene expression levels.1) Flotho et al. reported that Zeb did not regulate the expression levels of a large number of mRNAs or markers for genome-wide methylation.1) We previously showed that DAC suppressed invasion activity with the up-regulation of epithelial cell marker expression levels not only in parental SW620 cells, high-invasive colorectal cancer (CRC) cells, but also in oxaliplatin (L-OHP)-resistant SW620 (SW620/OxR) cells. 2)Pakneshan et al. demonstrated that AC enhanced invasion activity by up-regulating the urokinase plasminogen activator in prostate cancer.3) However, information on the effects of Zeb on invasion activity is limited.MicroRNAs (miRNAs), small non-coding RNAs that suppress target mRNA, play important roles in cancer metastasis. Members of the let-7 family (let-7a, let-7b, let-7c, let-7d, let-7e, let-7f, let-7g, and let-7i in addition to miR-98 and miR-202) are tumor suppressor miRNAs. 4) Kang et al. previously reported that let-7b suppressed invasion activity in gastric cancer.5) In addition, Kahlert et al. showed that let-7b expression level in CRC tumor invasion front was lower than that in CRC tumor center.6) The expression levels of let-7 family members are also regulated by DNA methylation. The location of let-7b is in the 3′-untranslated region of MIRLET7BHG as a long intergenic noncoding RNA. 7) Nishi et al. found that intracellular expression level of let-7b may be regulated by the DNA methylation status of CpG islands near transcription start site (TSS) of MIRLET7BHG.7) Kobayashi et al. showed that let-7 family members were more abundant in exosomes, small membrane vesicles of approximately 100 nm in diameter, from high-invasive ovarian cancer cells than in those from low-invasive ovarian cancer cells.8) In addition, Wong et al. reported that the expression levels of let-7 family members were upregulated by Zeb in nasopharyngeal carcinoma cells. We previously demonstrated that the invasion activ...

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Section: Discussionsupporting

confidence: 88%

Section: Methodsmentioning

confidence: 99%

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Effects of Zebularine on Invasion Activity and Intracellular Expression Level of let-7b in Colorectal Cancer Cells

Tanaka

Hosokawa

Matsumura

et al. 2017

Biological & Pharmaceutical Bulletin

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“…in the present study, we observed that expression of 10 miRNAs decreased significantly in the exosome derived from chemoresistance prostate cancer cells compared to their parental cells. Downregulated expression of miR-141 plays a role in selective resistance to L-OHP and epithelial-mesenchymal transition (EMT) in CRCs during repeated treatments with L-OHP (25). miR-429 were downregulated in drugresistant epithelial ovarian cancer tissues (26).…”

Section: Discussionmentioning

confidence: 99%

Exosome-derived microRNAs contribute to prostate cancer chemoresistance

Yang

Guan

et al. 2016

International Journal of Oncology

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Abstract. Certain microRNAs (miRNAs) play a key role in cancer cell chemoresistance. However, the pleiotropic functions of exosome-derived miRNAs on developing chemoresistance remain unknown. In the present study, we aimed to construct potential networks of miRNAs, which derived from the exosome of chemoresistant prostate cancer (PCa) cells, with their known target genes using miRNA expression profiling and bioinformatic tools. Global miRNA expression profiles were measured by microarray. Twelve miRNAs were initially selected and validated by qRT-PCR. Known targets of deregulated miRNAs were utilized using DIANA-TarBase database v6.0. The incorporation of deregulated miRNAs and target genes into KEGG pathways were utilized using DIANA-mirPath software. To construct potential miRNA regulatory networks, the overlapping parts of miRNAs and their targer genes from the selected KEGG pathway 'PCa progression (hsa05215)' were visualized by Cytoscape software. We identified 29 deregulated miRNAs, including 19 upregulated and 10 downregulated, in exosome samples derived from two kinds of paclitaxel resistance PCa cells (PC3-TXR and DU145-TXR) compared with their parental cells (PC3 and DU145). The enrichment results of deregulated miRNAs and known target genes showed that a few pathways were correlated with several critical cell signaling pathways. We found that hub hsa-miR3176, -141-3p, -5004-5p, -16-5p, -3915, -488-3p, -23c, -3673 and -3654 were potential targets to hub gene androgen receptor (AR) and phosphatase and tensin homolog (PTEN). Hub gene T-cell factors/lymphoid enhancer-binding factors 4 (TCF4) target genes were mainly regulated by hub hsa-miR-32-5, -141-3p, -606, -381 and -429. These results may provide a linkage between PCa chemoresistance and exosome regulatory networks and thus lead us to propose that AR, PTEN and TCF4 genes may be the important genes which are regulated by exosome miRNAs in chemoresistance cancer cells.

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“…5,6) Recent studies have reported that the EMT has been strongly associated with cancer cell stemness 7,8) and chemoresistance to anti-cancer drugs, [9][10][11][12] indicating that targeting EMT could be a good strategy to overcome cancer metastasis. Notably, transforming growth factor-β1 (TGF-β1) has been known to be a primary inducer of EMT both during developmental process and cancer progression.…”

mentioning

confidence: 99%

Nano-biomechanical Validation of Epithelial–Mesenchymal Transition in Oral Squamous Cell Carcinomas

Park

Jang

Jeong

2016

Biological & Pharmaceutical Bulletin

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The effective cure for oral squamous cell carcinoma (OSCC) patients is challenging due late diagnosis and fatal metastasis. The standard diagnosis for OSCC often depends on the subjective interpretation of conventional histopathology. Additionally, there is no standard way for OSCC prognosis. Over the past decade, nano-mechanical stiffness has been considered as a quantitative measure for cancer diagnosis. Nevertheless, its application to OSCC diagnosis and prognosis is still in a primitive stage. In this study, we investigated whether the OSCC progression can be predicted by nano-mechanical properties in combination with biochemical properties, especially the epithelial-mesenchymal transition (EMT). Atomic force microscopy-based nano-mechanical measurements of three different OSCC cell lines-SCC-4, SCC-9, and SCC-15-were conducted together with biochemical analyses. The gradual upregulation of Snail2, N-cadherin, and vimentin and the simultaneous downregulation of E-cadherin were observed, and the degree of upregulation and downregulation was stronger in the order of the cell lines mentioned above. The strength of enhancement in migration was in the same order as well. Consistently, nano-mechanical stiffness was gradually decreased as the EMT progresses. These results suggest that the nano-mechanical assay could serve as a quantitative tool to predict the OSCC progression in the context of the EMT. Furthermore, we found that the upregulated vimentin, a major filamentous component of the cytoskeleton, may contribute to mechanical softening, which can be discerned from the role of actin filaments in mechanical stiffness. In conclusion, our combinational study proposes a novel way to elucidate the mechanism of OSCC progression and its therapeutic targets.Key words nano-mechanics; epithelial-mesenchymal transition; atomic force microscopy; oral cancer Oral squamous cell carcinoma (OSCC) is the most common neoplasm of the head and neck squamous cell carcinoma (HNSCC), which represents approximately 6% of all types of cancer. Also about half a million new cases are diagnosed every year.1) It is a highly invasive malignant tumor characterized by a high rate of metastasis to the cervical lymph nodes.2) Diagnosis and management of OSCC have improved by combining therapies such as radical surgery, radiotherapy and neo-adjuvant chemotherapy, but the overall 5-year survival rate is still below 50% because of late diagnosis and high rate of recurrence.3,4) Thus, it is highly desirable to understand the underlying mechanism governing metastatic dissemination of OSCC for the development of anticancer therapeutics.The progression of OSCC is largely dependent on the epithelial-mesenchymal transition (EMT). 5,6) Recent studies have reported that the EMT has been strongly associated with cancer cell stemness 7,8) and chemoresistance to anti-cancer drugs, [9][10][11][12] indicating that targeting EMT could be a good strategy to overcome cancer metastasis. Notably, transforming growth factor-β1 (TGF-β1) has been known to be a prima...

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Induction of Epithelial-Mesenchymal Transition and Down-Regulation of miR-200c and miR-141 in Oxaliplatin-Resistant Colorectal Cancer Cells

Cited by 61 publications

References 34 publications

Effects of Zebularine on Invasion Activity and Intracellular Expression Level of let-7b in Colorectal Cancer Cells

Effects of Zebularine on Invasion Activity and Intracellular Expression Level of let-7b in Colorectal Cancer Cells

Exosome-derived microRNAs contribute to prostate cancer chemoresistance

Nano-biomechanical Validation of Epithelial–Mesenchymal Transition in Oral Squamous Cell Carcinomas

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