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miR-135b Promotes Cancer Progression by Targeting Transforming Growth Factor Beta Receptor II (TGFBR2) in Colorectal Cancer.

Li J, Liang H, Bai M, Ning T, Wang C, Fan Q, Wang Y, Fu Z, Wang N, Liu R, Zen K, Zhang CY, Chen X, Ba Y - PLoS ONE (2015)

Bottom Line: In this study, we found that the TGFBR2 protein levels were consistently upregulated in CRC tissues, whereas its mRNA levels varied in these tissues, suggesting that a post-transcriptional mechanism is involved in the regulation of TGFBR2.We demonstrated that miR-135b exerted a tumor-promoting effect by inducing the proliferation and inhibiting the apoptosis of CRC cells via the negative regulation of TGFBR2 expression.Taken together, our findings provide the first evidence supporting the role of miR-135b as an oncogene in CRC via the inhibition of TGFBR2 translation.

View Article: PubMed Central - PubMed

Affiliation: Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tiyuanbei, Tianjin, 300060, China; Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210093, China.

ABSTRACT
The transforming growth factor beta (TGF-β) signaling pathway is a tumor-suppressor pathway that is commonly inactivated in colorectal cancer (CRC). The inactivation of TGFBR2 is the most common genetic event affecting the TGF-β signaling pathway. However, the mechanism by which cancer cells downregulate TGFBR2 is unclear. In this study, we found that the TGFBR2 protein levels were consistently upregulated in CRC tissues, whereas its mRNA levels varied in these tissues, suggesting that a post-transcriptional mechanism is involved in the regulation of TGFBR2. Because microRNAs (miRNAs) are powerful post-transcriptional regulators of gene expression, we performed bioinformatic analyses to search for miRNAs that potentially target TGFBR2. We identified the specific targeting site of miR-135b in the 3'-untranslated region (3'-UTR) of TGFBR2. We further identified an inverse correlation between the levels of miR-135b and TGFBR2 protein, but not mRNA, in CRC tissue samples. By overexpressing or silencing miR-135b in CRC cells, we experimentally validated that miR-135b directly binds to the 3'-UTR of the TGFBR2 transcript and regulates TGFBR2 expression. Furthermore, the biological consequences of the targeting of TGFBR2 by miR-135b were examined using in vitro cell proliferation and apoptosis assays. We demonstrated that miR-135b exerted a tumor-promoting effect by inducing the proliferation and inhibiting the apoptosis of CRC cells via the negative regulation of TGFBR2 expression. Taken together, our findings provide the first evidence supporting the role of miR-135b as an oncogene in CRC via the inhibition of TGFBR2 translation.

No MeSH data available.


Related in: MedlinePlus

Upregulation of the TGFBR2 protein, but not mRNA, in CRC tissues.(A and B) Western blot analysis of the TGFBR2 protein levels in five paired CRC and normal adjacent tissue (NAT) samples. A: representative image; B: quantitative analysis. (C) Quantitative RT-PCR analysis of the TGFBR2 mRNA levels in five paired CRC and NAT tissue samples. * P < 0.05; ** P < 0.01; *** P < 0.001.
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pone.0130194.g001: Upregulation of the TGFBR2 protein, but not mRNA, in CRC tissues.(A and B) Western blot analysis of the TGFBR2 protein levels in five paired CRC and normal adjacent tissue (NAT) samples. A: representative image; B: quantitative analysis. (C) Quantitative RT-PCR analysis of the TGFBR2 mRNA levels in five paired CRC and NAT tissue samples. * P < 0.05; ** P < 0.01; *** P < 0.001.

Mentions: We first determined the expression patterns of TGFBR2 in human CRC tissues. After measuring the protein levels of TGFBR2 in five paired CRC and normal adjacent tissues, we found that the TGFBR2 protein levels were dramatically reduced in the CRC tissues compared to the normal adjacent tissues (Fig 1A and 1B). However, although the TGFBR2 protein was consistently downregulated in the CRC tissue, the TGFBR2 mRNA levels did not significantly differ between the cancerous and noncancerous tissues (Fig 1C). This disparity between the protein and mRNA expression of TGFBR2 in CRC strongly suggests that a post-transcriptional mechanism is involved in the regulation of TGFBR2.


miR-135b Promotes Cancer Progression by Targeting Transforming Growth Factor Beta Receptor II (TGFBR2) in Colorectal Cancer.

Li J, Liang H, Bai M, Ning T, Wang C, Fan Q, Wang Y, Fu Z, Wang N, Liu R, Zen K, Zhang CY, Chen X, Ba Y - PLoS ONE (2015)

Upregulation of the TGFBR2 protein, but not mRNA, in CRC tissues.(A and B) Western blot analysis of the TGFBR2 protein levels in five paired CRC and normal adjacent tissue (NAT) samples. A: representative image; B: quantitative analysis. (C) Quantitative RT-PCR analysis of the TGFBR2 mRNA levels in five paired CRC and NAT tissue samples. * P < 0.05; ** P < 0.01; *** P < 0.001.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4462589&req=5

pone.0130194.g001: Upregulation of the TGFBR2 protein, but not mRNA, in CRC tissues.(A and B) Western blot analysis of the TGFBR2 protein levels in five paired CRC and normal adjacent tissue (NAT) samples. A: representative image; B: quantitative analysis. (C) Quantitative RT-PCR analysis of the TGFBR2 mRNA levels in five paired CRC and NAT tissue samples. * P < 0.05; ** P < 0.01; *** P < 0.001.
Mentions: We first determined the expression patterns of TGFBR2 in human CRC tissues. After measuring the protein levels of TGFBR2 in five paired CRC and normal adjacent tissues, we found that the TGFBR2 protein levels were dramatically reduced in the CRC tissues compared to the normal adjacent tissues (Fig 1A and 1B). However, although the TGFBR2 protein was consistently downregulated in the CRC tissue, the TGFBR2 mRNA levels did not significantly differ between the cancerous and noncancerous tissues (Fig 1C). This disparity between the protein and mRNA expression of TGFBR2 in CRC strongly suggests that a post-transcriptional mechanism is involved in the regulation of TGFBR2.

Bottom Line: In this study, we found that the TGFBR2 protein levels were consistently upregulated in CRC tissues, whereas its mRNA levels varied in these tissues, suggesting that a post-transcriptional mechanism is involved in the regulation of TGFBR2.We demonstrated that miR-135b exerted a tumor-promoting effect by inducing the proliferation and inhibiting the apoptosis of CRC cells via the negative regulation of TGFBR2 expression.Taken together, our findings provide the first evidence supporting the role of miR-135b as an oncogene in CRC via the inhibition of TGFBR2 translation.

View Article: PubMed Central - PubMed

Affiliation: Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tiyuanbei, Tianjin, 300060, China; Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210093, China.

ABSTRACT
The transforming growth factor beta (TGF-β) signaling pathway is a tumor-suppressor pathway that is commonly inactivated in colorectal cancer (CRC). The inactivation of TGFBR2 is the most common genetic event affecting the TGF-β signaling pathway. However, the mechanism by which cancer cells downregulate TGFBR2 is unclear. In this study, we found that the TGFBR2 protein levels were consistently upregulated in CRC tissues, whereas its mRNA levels varied in these tissues, suggesting that a post-transcriptional mechanism is involved in the regulation of TGFBR2. Because microRNAs (miRNAs) are powerful post-transcriptional regulators of gene expression, we performed bioinformatic analyses to search for miRNAs that potentially target TGFBR2. We identified the specific targeting site of miR-135b in the 3'-untranslated region (3'-UTR) of TGFBR2. We further identified an inverse correlation between the levels of miR-135b and TGFBR2 protein, but not mRNA, in CRC tissue samples. By overexpressing or silencing miR-135b in CRC cells, we experimentally validated that miR-135b directly binds to the 3'-UTR of the TGFBR2 transcript and regulates TGFBR2 expression. Furthermore, the biological consequences of the targeting of TGFBR2 by miR-135b were examined using in vitro cell proliferation and apoptosis assays. We demonstrated that miR-135b exerted a tumor-promoting effect by inducing the proliferation and inhibiting the apoptosis of CRC cells via the negative regulation of TGFBR2 expression. Taken together, our findings provide the first evidence supporting the role of miR-135b as an oncogene in CRC via the inhibition of TGFBR2 translation.

No MeSH data available.


Related in: MedlinePlus