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MicroRNA-127-5p targets the biliverdin reductase B/nuclear factor-κB pathway to suppress cell growth in hepatocellular carcinoma cells.

Huan L, Bao C, Chen D, Li Y, Lian J, Ding J, Huang S, Liang L, He X - Cancer Sci. (2016)

Bottom Line: While exploring the mechanism of the inhibition of NF-κB activity by miR-127-5p, we found that miR-127-5p decreased the phosphorylation of p65.MicroRNA-127-5p inhibited the growth and colony formation of hepatocellular carcinoma (HCC) cells and decreased biliverdin reductase B (BLVRB) expression by directly binding to its 3'-UTR.In summary, we found that miR-127-5p suppressed NF-κB activity by directly targeting BLVRB in HCC cells, and this finding improves our understanding of the molecular mechanism of inflammation-induced HCC growth and proliferation and the successful inhibition of NF-κB activity by cancer treatment.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

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MicroRNA (miR)‐127‐5p is frequently downregulated in hepatocellular carcinoma (HCC). (a) The expression level of miR‐127‐5p was determined using data from The Cancer Genome Atlas (http://cancergenome.nih.gov/). The expression level of miR‐127‐5p in 47 pairs of HCC tissues and matching adjacent normal tissues. Data are presented as log2 fold change. (b) Significant downregulation of miR‐127‐5p expression in HCC samples compared to paired adjacent normal tissue samples was observed. (c) Pie chart of the proportions of HCC samples in which miR‐127‐5p expression was upregulated (red), downregulated (blue), or unchanged (green). (d) HCC samples with poor histological grade have lower miR‐127‐5p expression than samples with higher histological grade. *P < 0.05, ***P < 0.001.
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cas12869-fig-0002: MicroRNA (miR)‐127‐5p is frequently downregulated in hepatocellular carcinoma (HCC). (a) The expression level of miR‐127‐5p was determined using data from The Cancer Genome Atlas (http://cancergenome.nih.gov/). The expression level of miR‐127‐5p in 47 pairs of HCC tissues and matching adjacent normal tissues. Data are presented as log2 fold change. (b) Significant downregulation of miR‐127‐5p expression in HCC samples compared to paired adjacent normal tissue samples was observed. (c) Pie chart of the proportions of HCC samples in which miR‐127‐5p expression was upregulated (red), downregulated (blue), or unchanged (green). (d) HCC samples with poor histological grade have lower miR‐127‐5p expression than samples with higher histological grade. *P < 0.05, ***P < 0.001.

Mentions: As miR‐127‐5p inhibited the activation of NF‐κB in HCC cells, we wondered whether miR‐127‐5p could act as a tumor suppressor in HCC. Therefore, we investigated the expression of miR‐127‐5p in HCC samples reported in the Cancer Genome Atlas (http://cancergenome.nih.gov/) database. Compared to normal liver, miR‐127‐5p expression is lower in HCC tissues (Fig. 2a,b, Table 1). Downregulation of miR‐127‐5p (greater than twofold change) was observed in 58% (27/47) of HCC tissues compared to matched adjacent normal tissues (Fig. 2c). In addition, HCC tissues with poor histologic grade showed significantly lower expression of miR‐127‐5p than tissues with higher histologic grade (Fig. 2d, Table S1). These results, together with the known function of miR‐127‐5p, indicate that miR‐127‐5p is a potential tumor suppressor in HCC. Furthermore, we found that miR‐127‐5p mimic suppressed the growth of SMMC‐7721 and SNU‐449 cells (Fig. 3a). Moreover, stable expression of miR‐127‐5p through a lentiviral system also decreased the growth of both cell types (Fig. 3b). We also examined the effects of miR‐127‐5p on the colony formation ability of HCC cells and found that stable expression of miR‐127‐5p significantly reduced the colony formation ability of SMMC‐7721 and SNU‐449 cells (Fig. 3c).


MicroRNA-127-5p targets the biliverdin reductase B/nuclear factor-κB pathway to suppress cell growth in hepatocellular carcinoma cells.

Huan L, Bao C, Chen D, Li Y, Lian J, Ding J, Huang S, Liang L, He X - Cancer Sci. (2016)

MicroRNA (miR)‐127‐5p is frequently downregulated in hepatocellular carcinoma (HCC). (a) The expression level of miR‐127‐5p was determined using data from The Cancer Genome Atlas (http://cancergenome.nih.gov/). The expression level of miR‐127‐5p in 47 pairs of HCC tissues and matching adjacent normal tissues. Data are presented as log2 fold change. (b) Significant downregulation of miR‐127‐5p expression in HCC samples compared to paired adjacent normal tissue samples was observed. (c) Pie chart of the proportions of HCC samples in which miR‐127‐5p expression was upregulated (red), downregulated (blue), or unchanged (green). (d) HCC samples with poor histological grade have lower miR‐127‐5p expression than samples with higher histological grade. *P < 0.05, ***P < 0.001.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4814244&req=5

cas12869-fig-0002: MicroRNA (miR)‐127‐5p is frequently downregulated in hepatocellular carcinoma (HCC). (a) The expression level of miR‐127‐5p was determined using data from The Cancer Genome Atlas (http://cancergenome.nih.gov/). The expression level of miR‐127‐5p in 47 pairs of HCC tissues and matching adjacent normal tissues. Data are presented as log2 fold change. (b) Significant downregulation of miR‐127‐5p expression in HCC samples compared to paired adjacent normal tissue samples was observed. (c) Pie chart of the proportions of HCC samples in which miR‐127‐5p expression was upregulated (red), downregulated (blue), or unchanged (green). (d) HCC samples with poor histological grade have lower miR‐127‐5p expression than samples with higher histological grade. *P < 0.05, ***P < 0.001.
Mentions: As miR‐127‐5p inhibited the activation of NF‐κB in HCC cells, we wondered whether miR‐127‐5p could act as a tumor suppressor in HCC. Therefore, we investigated the expression of miR‐127‐5p in HCC samples reported in the Cancer Genome Atlas (http://cancergenome.nih.gov/) database. Compared to normal liver, miR‐127‐5p expression is lower in HCC tissues (Fig. 2a,b, Table 1). Downregulation of miR‐127‐5p (greater than twofold change) was observed in 58% (27/47) of HCC tissues compared to matched adjacent normal tissues (Fig. 2c). In addition, HCC tissues with poor histologic grade showed significantly lower expression of miR‐127‐5p than tissues with higher histologic grade (Fig. 2d, Table S1). These results, together with the known function of miR‐127‐5p, indicate that miR‐127‐5p is a potential tumor suppressor in HCC. Furthermore, we found that miR‐127‐5p mimic suppressed the growth of SMMC‐7721 and SNU‐449 cells (Fig. 3a). Moreover, stable expression of miR‐127‐5p through a lentiviral system also decreased the growth of both cell types (Fig. 3b). We also examined the effects of miR‐127‐5p on the colony formation ability of HCC cells and found that stable expression of miR‐127‐5p significantly reduced the colony formation ability of SMMC‐7721 and SNU‐449 cells (Fig. 3c).

Bottom Line: While exploring the mechanism of the inhibition of NF-κB activity by miR-127-5p, we found that miR-127-5p decreased the phosphorylation of p65.MicroRNA-127-5p inhibited the growth and colony formation of hepatocellular carcinoma (HCC) cells and decreased biliverdin reductase B (BLVRB) expression by directly binding to its 3'-UTR.In summary, we found that miR-127-5p suppressed NF-κB activity by directly targeting BLVRB in HCC cells, and this finding improves our understanding of the molecular mechanism of inflammation-induced HCC growth and proliferation and the successful inhibition of NF-κB activity by cancer treatment.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Show MeSH
Related in: MedlinePlus