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Low mir-372 expression correlates with poor prognosis and tumor metastasis in hepatocellular carcinoma.

Wu G, Wang Y, Lu X, He H, Liu H, Meng X, Xia S, Zheng K, Liu B - BMC Cancer (2015)

Bottom Line: However, results have been conflicting regarding its expression levels and role in HCC.Prognostic significance was analyzed by the Kaplan-Meier survival method and Cox regression. miR-372 was expressed at lower levels in HCC tissues compared with controls and was related to tumor metastasis and poor prognosis.Hypermethylation of miR-372 was detected in HCC cell lines and tissues, and miR-372 expression was restored upon 5-aza-dCyd treatment.

View Article: PubMed Central - PubMed

Affiliation: Department of General Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, 110001, China. wgzwl@hotmail.com.

ABSTRACT

Background: Recent studies have shown that miR-372 plays important roles in hepatocellular carcinoma (HCC) progression. However, results have been conflicting regarding its expression levels and role in HCC.

Methods: RT-PCR and in situ hybridization was used to evaluate miR-372 expression in HCC tissues and cell lines. The methylation status of neighboring CpG islands upstream of the miR-372 promoter was analyzed by methylation-specific PCR (MSP). Transfection of miR-372 mimic into HCC cell lines was used to evaluate cellular proliferation and invasion. Prognostic significance was analyzed by the Kaplan-Meier survival method and Cox regression.

Results: miR-372 was expressed at lower levels in HCC tissues compared with controls and was related to tumor metastasis and poor prognosis. Hypermethylation of miR-372 was detected in HCC cell lines and tissues, and miR-372 expression was restored upon 5-aza-dCyd treatment. Upregulated expression by mir-372 mimic transfection inhibited proliferation and invasion capacity in HCC cells.

Conclusions: miR-372 may play an important role in hepatic carcinogenesis and may serve as a new target or method to detect and treat HCC in the future.

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Related in: MedlinePlus

Four HCC cell lines (HUH7, HCCLM3, SMMC7721, LO2) were treated with 5-aza-dCyd, a methyltransferase inhibitor and the miRNA expression levels were assayed using TaqMan miRNA PCR. The expression of mir-372 was restored with 5-aza-dCyd treatment in HUH7 and HCCLM3 cell lines (*P < 0.05,**P < 0.01) and the mir-372 DNA methylation level was inhibited. Treatment with a histone deacetylase inhibitor, TSA, had no influence on the expression of mir-372 in all four cell lines.
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Fig5: Four HCC cell lines (HUH7, HCCLM3, SMMC7721, LO2) were treated with 5-aza-dCyd, a methyltransferase inhibitor and the miRNA expression levels were assayed using TaqMan miRNA PCR. The expression of mir-372 was restored with 5-aza-dCyd treatment in HUH7 and HCCLM3 cell lines (*P < 0.05,**P < 0.01) and the mir-372 DNA methylation level was inhibited. Treatment with a histone deacetylase inhibitor, TSA, had no influence on the expression of mir-372 in all four cell lines.

Mentions: We then assessed the effects of demethylation on the expression of miR-372. Four HCC cell lines (HUH7, HCCLM3, SMMC7721, LO2) were treated with 5-aza-dCyd, a methyltransferase inhibitor, and the miRNA expression levels were assayed using TaqMan miRNA PCR. The expression of miR-372 was restored with 5-aza-dCyd treatment in HUH7 and HCCLM3 cell lines and the miR-372 DNA methylation level was inhibited (Figure 5), suggesting that aberrant DNA methylation suppressed the expression of mir-372. Treatment with a histone deacetylase inhibitor, TSA, had no influence on the expression of miR-372 in all four cell lines (Figure 5). These findings suggest that histone deacetylation may not contribute to the transcriptional repression of miR-372.Figure 5


Low mir-372 expression correlates with poor prognosis and tumor metastasis in hepatocellular carcinoma.

Wu G, Wang Y, Lu X, He H, Liu H, Meng X, Xia S, Zheng K, Liu B - BMC Cancer (2015)

Four HCC cell lines (HUH7, HCCLM3, SMMC7721, LO2) were treated with 5-aza-dCyd, a methyltransferase inhibitor and the miRNA expression levels were assayed using TaqMan miRNA PCR. The expression of mir-372 was restored with 5-aza-dCyd treatment in HUH7 and HCCLM3 cell lines (*P < 0.05,**P < 0.01) and the mir-372 DNA methylation level was inhibited. Treatment with a histone deacetylase inhibitor, TSA, had no influence on the expression of mir-372 in all four cell lines.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4379970&req=5

Fig5: Four HCC cell lines (HUH7, HCCLM3, SMMC7721, LO2) were treated with 5-aza-dCyd, a methyltransferase inhibitor and the miRNA expression levels were assayed using TaqMan miRNA PCR. The expression of mir-372 was restored with 5-aza-dCyd treatment in HUH7 and HCCLM3 cell lines (*P < 0.05,**P < 0.01) and the mir-372 DNA methylation level was inhibited. Treatment with a histone deacetylase inhibitor, TSA, had no influence on the expression of mir-372 in all four cell lines.
Mentions: We then assessed the effects of demethylation on the expression of miR-372. Four HCC cell lines (HUH7, HCCLM3, SMMC7721, LO2) were treated with 5-aza-dCyd, a methyltransferase inhibitor, and the miRNA expression levels were assayed using TaqMan miRNA PCR. The expression of miR-372 was restored with 5-aza-dCyd treatment in HUH7 and HCCLM3 cell lines and the miR-372 DNA methylation level was inhibited (Figure 5), suggesting that aberrant DNA methylation suppressed the expression of mir-372. Treatment with a histone deacetylase inhibitor, TSA, had no influence on the expression of miR-372 in all four cell lines (Figure 5). These findings suggest that histone deacetylation may not contribute to the transcriptional repression of miR-372.Figure 5

Bottom Line: However, results have been conflicting regarding its expression levels and role in HCC.Prognostic significance was analyzed by the Kaplan-Meier survival method and Cox regression. miR-372 was expressed at lower levels in HCC tissues compared with controls and was related to tumor metastasis and poor prognosis.Hypermethylation of miR-372 was detected in HCC cell lines and tissues, and miR-372 expression was restored upon 5-aza-dCyd treatment.

View Article: PubMed Central - PubMed

Affiliation: Department of General Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, 110001, China. wgzwl@hotmail.com.

ABSTRACT

Background: Recent studies have shown that miR-372 plays important roles in hepatocellular carcinoma (HCC) progression. However, results have been conflicting regarding its expression levels and role in HCC.

Methods: RT-PCR and in situ hybridization was used to evaluate miR-372 expression in HCC tissues and cell lines. The methylation status of neighboring CpG islands upstream of the miR-372 promoter was analyzed by methylation-specific PCR (MSP). Transfection of miR-372 mimic into HCC cell lines was used to evaluate cellular proliferation and invasion. Prognostic significance was analyzed by the Kaplan-Meier survival method and Cox regression.

Results: miR-372 was expressed at lower levels in HCC tissues compared with controls and was related to tumor metastasis and poor prognosis. Hypermethylation of miR-372 was detected in HCC cell lines and tissues, and miR-372 expression was restored upon 5-aza-dCyd treatment. Upregulated expression by mir-372 mimic transfection inhibited proliferation and invasion capacity in HCC cells.

Conclusions: miR-372 may play an important role in hepatic carcinogenesis and may serve as a new target or method to detect and treat HCC in the future.

Show MeSH
Related in: MedlinePlus