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miR-34a screened by miRNA profiling negatively regulates Wnt/β-catenin signaling pathway in Aflatoxin B1 induced hepatotoxicity.

Zhu L, Gao J, Huang K, Luo Y, Zhang B, Xu W - Sci Rep (2015)

Bottom Line: Here, we applied Illumina deep sequencing technology for high-throughout profiling of microRNAs in HepG2 cells lines after treatment with AFB1.Anti-miR-34a can significantly relieved the down-regulated β-catenin and its downstream genes, c-myc and Cyclin D1, and the S-phase arrest in cell cycle induced by AFB1 can also be relieved.These results suggested that AFB1 might down-regulate Wnt/β-catenin signaling pathway in HepG2 cells by up-regulating miR-34a, which may involve in the mechanism of liver tumorigenesis.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Food Safety, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China, 100083.

ABSTRACT
Aflatoxin-B1 (AFB1), a hepatocarcinogenic mycotoxin, was demonstrated to induce the high rate of hepatocellular carcinoma (HCC). MicroRNAs (miRNAs) participate in the regulation of several biological processes in HCC. However, the function of miRNAs in AFB1-induced HCC has received a little attention. Here, we applied Illumina deep sequencing technology for high-throughout profiling of microRNAs in HepG2 cells lines after treatment with AFB1. Analysis of the differential expression profile of miRNAs in two libraries, we identified 9 known miRNAs and 1 novel miRNA which exhibited abnormal expression. KEGG analysis indicated that predicted target genes of differentially expressed miRNAs are involved in cancer-related pathways. Down-regulated of Drosha, DGCR8 and Dicer 1 indicated an impairment of miRNA biogenesis in response to AFB1. miR-34a was up-regulated significantly, down-regulating the expression of Wnt/β-catenin signaling pathway by target gene β-catenin. Anti-miR-34a can significantly relieved the down-regulated β-catenin and its downstream genes, c-myc and Cyclin D1, and the S-phase arrest in cell cycle induced by AFB1 can also be relieved. These results suggested that AFB1 might down-regulate Wnt/β-catenin signaling pathway in HepG2 cells by up-regulating miR-34a, which may involve in the mechanism of liver tumorigenesis.

No MeSH data available.


Related in: MedlinePlus

Different miRNA expression in volcano diagram.The x axis stands for the fold change of different miRNAs. The Y axis stands for significant difference of miRNA expression changes. Every miRNA are represented with the dots. The blue dots indicate no significant difference miRNAs; The red dots indicate up-regulated miRNAs; The green dots mean down-regulated miRNAs.
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f4: Different miRNA expression in volcano diagram.The x axis stands for the fold change of different miRNAs. The Y axis stands for significant difference of miRNA expression changes. Every miRNA are represented with the dots. The blue dots indicate no significant difference miRNAs; The red dots indicate up-regulated miRNAs; The green dots mean down-regulated miRNAs.

Mentions: We further analyzed the differentially expressed miRNA between two conditions/groups using the DESeq2R package28. The read count data of the miRNA expression level was analyzed based on negative binomial distribution. Volcano Fig. 4 was used to show the global distribution of the differentially expressed miRNA, corrected P-value of 0.05 was set as the threshold for significantly differential expression by default (padj < 0.05) (Fig. 4).We used hierarchical cluster to analyze differentially expressed sRNA of every sample (Fig. 5). First we got a set of difference of miRNAs from each combination, then compared the TPM of every sample finite union from all the sets of differential expression miRNAs to make hierarchical cluster. The P-values was adjusted using the Benjamini & Hochberg method (padj < 0.05). The results showed that hsa-miR-19b, hsa-miR-19a, hsa-miR-34a, hsa-miR-99a, hsa-miR-190a and hsa-miR-16 were up-regulated as a result of AFB1 treatment compared to CK, while hsa-miR-1307, hsa-miR-99b, hsa-miR-100-5p showed the opposite trend (Table 2).


miR-34a screened by miRNA profiling negatively regulates Wnt/β-catenin signaling pathway in Aflatoxin B1 induced hepatotoxicity.

Zhu L, Gao J, Huang K, Luo Y, Zhang B, Xu W - Sci Rep (2015)

Different miRNA expression in volcano diagram.The x axis stands for the fold change of different miRNAs. The Y axis stands for significant difference of miRNA expression changes. Every miRNA are represented with the dots. The blue dots indicate no significant difference miRNAs; The red dots indicate up-regulated miRNAs; The green dots mean down-regulated miRNAs.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4645126&req=5

f4: Different miRNA expression in volcano diagram.The x axis stands for the fold change of different miRNAs. The Y axis stands for significant difference of miRNA expression changes. Every miRNA are represented with the dots. The blue dots indicate no significant difference miRNAs; The red dots indicate up-regulated miRNAs; The green dots mean down-regulated miRNAs.
Mentions: We further analyzed the differentially expressed miRNA between two conditions/groups using the DESeq2R package28. The read count data of the miRNA expression level was analyzed based on negative binomial distribution. Volcano Fig. 4 was used to show the global distribution of the differentially expressed miRNA, corrected P-value of 0.05 was set as the threshold for significantly differential expression by default (padj < 0.05) (Fig. 4).We used hierarchical cluster to analyze differentially expressed sRNA of every sample (Fig. 5). First we got a set of difference of miRNAs from each combination, then compared the TPM of every sample finite union from all the sets of differential expression miRNAs to make hierarchical cluster. The P-values was adjusted using the Benjamini & Hochberg method (padj < 0.05). The results showed that hsa-miR-19b, hsa-miR-19a, hsa-miR-34a, hsa-miR-99a, hsa-miR-190a and hsa-miR-16 were up-regulated as a result of AFB1 treatment compared to CK, while hsa-miR-1307, hsa-miR-99b, hsa-miR-100-5p showed the opposite trend (Table 2).

Bottom Line: Here, we applied Illumina deep sequencing technology for high-throughout profiling of microRNAs in HepG2 cells lines after treatment with AFB1.Anti-miR-34a can significantly relieved the down-regulated β-catenin and its downstream genes, c-myc and Cyclin D1, and the S-phase arrest in cell cycle induced by AFB1 can also be relieved.These results suggested that AFB1 might down-regulate Wnt/β-catenin signaling pathway in HepG2 cells by up-regulating miR-34a, which may involve in the mechanism of liver tumorigenesis.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Food Safety, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China, 100083.

ABSTRACT
Aflatoxin-B1 (AFB1), a hepatocarcinogenic mycotoxin, was demonstrated to induce the high rate of hepatocellular carcinoma (HCC). MicroRNAs (miRNAs) participate in the regulation of several biological processes in HCC. However, the function of miRNAs in AFB1-induced HCC has received a little attention. Here, we applied Illumina deep sequencing technology for high-throughout profiling of microRNAs in HepG2 cells lines after treatment with AFB1. Analysis of the differential expression profile of miRNAs in two libraries, we identified 9 known miRNAs and 1 novel miRNA which exhibited abnormal expression. KEGG analysis indicated that predicted target genes of differentially expressed miRNAs are involved in cancer-related pathways. Down-regulated of Drosha, DGCR8 and Dicer 1 indicated an impairment of miRNA biogenesis in response to AFB1. miR-34a was up-regulated significantly, down-regulating the expression of Wnt/β-catenin signaling pathway by target gene β-catenin. Anti-miR-34a can significantly relieved the down-regulated β-catenin and its downstream genes, c-myc and Cyclin D1, and the S-phase arrest in cell cycle induced by AFB1 can also be relieved. These results suggested that AFB1 might down-regulate Wnt/β-catenin signaling pathway in HepG2 cells by up-regulating miR-34a, which may involve in the mechanism of liver tumorigenesis.

No MeSH data available.


Related in: MedlinePlus