Locked Nucleic Acid <i>In situ</i> Hybridization Analysis of miR-21 Expression during Colorectal Cancer Development

Yamamichi, Nobutake; Shimomura, Ryoichi; Inada, Ken Ichi; Sakurai, Kouhei; Haraguchi, Takeshi; Ozaki, Yuka; Fujita, Shuji; Mizutani, Taketoshi; Furukawa, Chihiro; Fujishiro, Mitsuhiro; Ichinose, Masakazu; Shiogama, Kazuya; Tsutsumi, Yutaka; Omata, Masao; Iba, Hideo

doi:10.1158/1078-0432.ccr-08-3257

Cited by 166 publications

(127 citation statements)

References 41 publications

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“…The function of miRNA is the downregulation of multiple target gene expression by degrading the mRNA or blocking its translation into protein through RNA interference (24,25). Several miRNAs, such as miRNA-21 (miR-21), miR-17-92 cluster, and miR-135, were highly expressed in CRC tissues (26)(27)(28)(29). Several recent studies reported that the circulating miRNA in plasma was a potential marker for CRC detection (30,31) and was remarkably stable in plasma and protected from endogenous RNase activity (32).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA Expression Profiling of Exfoliated Colonocytes Isolated from Feces for Colorectal Cancer Screening

Koga

Yasunaga

Takahashi

et al. 2010

Cancer Prevention Research

189

156

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To reduce the colorectal cancer (CRC) mortality rate, we have reported several CRC screening methods using colonocytes isolated from feces. Expression analysis of oncogenic microRNA (miRNA) in peripheral blood was recently reported for CRC detection. In the present study, we conducted miRNA expression analysis of exfoliated colonocytes isolated from feces for CRC screening. Two hundred six CRC patients and 134 healthy volunteers were enrolled in the study. miRNA expression of the miR-17-92 cluster, miR-21, and miR-135 in colonocytes isolated from feces as well as frozen tissues was analyzed by quantitative realtime PCR. The expression of the miR-17-92 cluster, miR-21, and miR-135 was significantly higher in CRC tissues compared with normal tissues. The exfoliated colonocytes of 197 CRC patients and 119 healthy volunteers were analyzed because of the presence of sufficient miRNA concentration. miR-21 expression did not differ significantly between CRC patients and healthy volunteers (P = 0.6). The expression of miR-17-92 cluster and miR-135 was significantly higher in CRC patients than in healthy volunteers (P < 0.0001). The overall sensitivity and specificity by using miRNA expression was 74.1% (146/197; 95% confidence interval, 67.4-80.1) and 79.0% (94/119; 95% confidence interval, 70.6-85.9), respectively. Sensitivity was dependent only on tumor location (P = 0.0001). miRNA was relatively well conserved in exfoliated colonocytes from feces both of CRC patients and healthy volunteers. miRNA expression analysis of the isolated colonocytes may be a useful method for CRC screening. Furthermore, oncogenic miRNA highly expressed in CRC should be investigated for CRC screening tests in the future. Cancer Prev Res; 3(11); 1435-42. ©2010 AACR.

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Section: Introductionmentioning

confidence: 99%

MicroRNA Expression Profiling of Exfoliated Colonocytes Isolated from Feces for Colorectal Cancer Screening

Koga

Yasunaga

Takahashi

et al. 2010

Cancer Prevention Research

189

156

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“…An increasing number of reports on the clinical significance of miRNAs in various types of cancer, including CRC, have been published. Differences in expression levels between CRC and normal colorectal tissue have been described (12)(13)(14), and certain studies have also provided evidence of prognostic (15,16) and predictive (17) value related to miRNAs.…”

Section: Introductionmentioning

confidence: 99%

Elevated microRNA-126 is associated with high vascular endothelial growth factor receptor 2 expression levels and high microvessel density in colorectal cancer

Hansen

Andersen

Nielsen³

et al. 2011

Oncology Letters

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Abstract. MicroRNAs (miRNAs) are involved in a number of biological processes, including tumour biology. Pre-clinical studies have shown that miRNA-126 regulates signalling downstream of vascular endothelial growth factor receptor 2 (VEGFR-2) and, consequently, angiogenesis. The aim of this study was to analyse the possible relationship between miRNA-126, VEGFR-2 and angiogenesis in tumour tissue from patients with colorectal cancer (CRC). Tumour tissue was obtained from 81 patients. The miRNA-126 and VEGFR-2 gene expression levels were analysed by PCR and the protein concentrations of VEGFR-2 were analysed by ELISA. Angiogenesis, visualised by the endothelial cell marker CD105 combined with caldesmon, was assessed by immunohistochemistry and the microvessel density (MVD) technique. In situ hybridisation was performed for miRNA-126. Tumours were classified as low or high miRNA-126-expressing using the median as the cut-off. The median gene expression levels of VEGFR-2 were significantly lower in the tumours expressing low levels of miRNA-126, 0.30 (95% CI, 0.24-0.36), compared to those expressing high levels of miRNA-126, 0.48 (95% CI, 0.28-0.60), p=0.02. A positive association was observed with VEGFR-2 protein concentrations, p=0.06. The median MVD was significantly lower in the tumours expressing low levels of 5.8 (95% CI,), compared to those expressing high levels, 8.0 (95% CI, 6.33-9.00), p<0.01. miRNA-126 was detected in endothelial cells by in situ hybridisation analysis. These results suggest that high levels of miRNA-126 in CRC are associated with high VEGFR-2 mRNA and protein levels and a higher density of newly formed microvessels. However, further studies should be conducted to analyse the clinical value of miRNA-126 in CRC.

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“…Our data demonstrating that tumor-derived cell lines cultured under standardized conditions fail to overexpress miR-21 could explain why in colon cancer two studies in cell lines found that the tumor/normal ratio of miR-21 is negative (33) or low (34), while in contrast reports analyzing miR-21 in colorectal cancer tissue showed that miR-21 levels are significantly increased in the tumor (8,9). Therefore, we conclude that the tissue-specific tumor environment might be necessary for miR-21 elevation.…”

Section: Discussionmentioning

confidence: 76%

“…Elevated miR-21 expression in cancer cells compared to the normal control cells were observed in almost all solid tumors (6) including head and neck (7), colorectal (8,9), lung (6,10), breast (11,12), esophageal (13) and liver cancer (14).…”

Section: Introductionmentioning

confidence: 99%

Expression of microRNA-21 in non-small cell lung cancer tissue increases with disease progression and is likely caused by growth conditional changes during malignant transformation

Haigl

Vanas

Setinek

et al. 2014

International Journal of Oncology

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Abstract. MicroRNAs can govern up to hundred different mRNAs and are important regulators of gene expression programs in development and disease. We analyzed the expression of microRNA-21, one of the most common oncomirs, in non-small cell lung cancer (NSCLC). Using northern blots the microRNA-21 expression levels of NSCLC-derived tissue and cell lines were measured. In line with earlier observations we show that mature microRNA-21 expression levels are highly increased in NSCLC-derived tissue compared to normal lung tissue. Additionally, we demonstrate that microRNA-21 levels correlate with malignancy since its expression in higher staged tumors is significantly more elevated compared to stage 1A. Interestingly, microRNA-21 levels in cultured NSCLC-derived cells are comparable to the expression detected in non-malignant lung tissue. Since microRNA-21 levels showed no fluctuation during the cell cycle, accelerated proliferation of tumor cells is not responsible for microRNA-21 upregulation in the tumor compartment. Similarly to NSCLC-derived cancer cells, the tumor-associated fibroblasts show low expression levels of microRNA-21. Together, these data indicate that rather microenviromental and growth conditional changes than intrinsic features of the cancer cells are responsible for the observed increase of microRNA-21 levels in tumor tissues. Subsequently culturing conditions were changed to assess the impact of co-cultivation with fibroblasts, hypoxia and anchorage-independent growth on microRNA-21 expression. While co-cultivation with tumor-associated fibroblasts had no effect on microRNA-21 expression, both hypoxia and anchorage-independent growth cause a microRNA-21 elevation. In summary, our data demonstrate that growth conditions especially expected in more malignant tumors result in microRNA-21 upregulation explaining the observed increase in higher staged lung cancer tissue, but not in lung cancerderived cells.

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Locked Nucleic Acid In situ Hybridization Analysis of miR-21 Expression during Colorectal Cancer Development

Cited by 166 publications

References 41 publications

MicroRNA Expression Profiling of Exfoliated Colonocytes Isolated from Feces for Colorectal Cancer Screening

MicroRNA Expression Profiling of Exfoliated Colonocytes Isolated from Feces for Colorectal Cancer Screening

Elevated microRNA-126 is associated with high vascular endothelial growth factor receptor 2 expression levels and high microvessel density in colorectal cancer

Expression of microRNA-21 in non-small cell lung cancer tissue increases with disease progression and is likely caused by growth conditional changes during malignant transformation

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