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microRNA-22, downregulated in hepatocellular carcinoma and correlated with prognosis, suppresses cell proliferation and tumourigenicity.

Zhang J, Yang Y, Yang T, Liu Y, Li A, Fu S, Wu M, Pan Z, Zhou W - Br. J. Cancer (2010)

Bottom Line: Furthermore, histone deacetylase 4 (HDAC4), known to have critical roles in cancer development, was proved to be directly targeted and regulated by miR-22.In addition, cell proliferation was also suppressed by knockdown of HDAC4 or treatment with HDAC inhibitor trichostatin A in HCC cell lines. miR-22, downregulated in HCC, has an anti-proliferative effect on HCC cells both in vitro and in vivo.Furthermore, miR-22 may have considerable potential in identification of the prognosis and application of cancer therapy for HCC patients.

View Article: PubMed Central - PubMed

Affiliation: The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.

ABSTRACT

Background: Recently, microRNAs in cancer development have attracted much attention, but their roles in tumorigenesis are still largely unknown. In this study, a functional role of miR-22 in hepatocellular carcinoma (HCC) development has been identified.

Methods: Quantitative real-time PCR was used to determine the level of miR-22 transcript in HCC clinical samples, and its correlation with disease-free survival was determined using Kaplan-Meier method. Restoration of miR-22 expression was carried out in HCC cell lines to assess its influence on HCC cell proliferation and tumourigenicity.

Results: In the 160 paired HCC tissue samples, miR-22 expression was downregulated in HCC, and low miR-22 expression in HCC was predictive of poor survival in HCC patients. Functional studies indicated that ectopic expression of miR-22 significantly inhibits HCC cell proliferation and tumourigenicity. Furthermore, histone deacetylase 4 (HDAC4), known to have critical roles in cancer development, was proved to be directly targeted and regulated by miR-22. Furthermore, HDAC4 was upregulated in miR-22-downregulated HCC tissues, suggesting that downregulation of miR-22 might participate in HCC carcinogenesis and progression through potentiation of HDAC4 expression. In addition, cell proliferation was also suppressed by knockdown of HDAC4 or treatment with HDAC inhibitor trichostatin A in HCC cell lines.

Conclusion: miR-22, downregulated in HCC, has an anti-proliferative effect on HCC cells both in vitro and in vivo. Furthermore, miR-22 may have considerable potential in identification of the prognosis and application of cancer therapy for HCC patients.

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Kaplan–Meier disease-free survival analysis for HCC patients according to miR-22 level. The median value of miR-22 level was chosen as the cutoff point for separating miR-22 low-expression tumours (n=80) from miR-22 high-expression cases (n=80). P-value is shown with the use of log-rank test in SPSS 17.0.
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fig3: Kaplan–Meier disease-free survival analysis for HCC patients according to miR-22 level. The median value of miR-22 level was chosen as the cutoff point for separating miR-22 low-expression tumours (n=80) from miR-22 high-expression cases (n=80). P-value is shown with the use of log-rank test in SPSS 17.0.

Mentions: Whether miR-22 downregulation correlates with prognosis of HCC patients was investigated further. As shown in Figure 3, the Kaplan–Meier method reveals that lower miR-22 expression level correlates with significantly reduced disease-free survival of the 160 HCC patients. This result further indicates the importance of miR-22 downregulation in HCC development.


microRNA-22, downregulated in hepatocellular carcinoma and correlated with prognosis, suppresses cell proliferation and tumourigenicity.

Zhang J, Yang Y, Yang T, Liu Y, Li A, Fu S, Wu M, Pan Z, Zhou W - Br. J. Cancer (2010)

Kaplan–Meier disease-free survival analysis for HCC patients according to miR-22 level. The median value of miR-22 level was chosen as the cutoff point for separating miR-22 low-expression tumours (n=80) from miR-22 high-expression cases (n=80). P-value is shown with the use of log-rank test in SPSS 17.0.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2967065&req=5

fig3: Kaplan–Meier disease-free survival analysis for HCC patients according to miR-22 level. The median value of miR-22 level was chosen as the cutoff point for separating miR-22 low-expression tumours (n=80) from miR-22 high-expression cases (n=80). P-value is shown with the use of log-rank test in SPSS 17.0.
Mentions: Whether miR-22 downregulation correlates with prognosis of HCC patients was investigated further. As shown in Figure 3, the Kaplan–Meier method reveals that lower miR-22 expression level correlates with significantly reduced disease-free survival of the 160 HCC patients. This result further indicates the importance of miR-22 downregulation in HCC development.

Bottom Line: Furthermore, histone deacetylase 4 (HDAC4), known to have critical roles in cancer development, was proved to be directly targeted and regulated by miR-22.In addition, cell proliferation was also suppressed by knockdown of HDAC4 or treatment with HDAC inhibitor trichostatin A in HCC cell lines. miR-22, downregulated in HCC, has an anti-proliferative effect on HCC cells both in vitro and in vivo.Furthermore, miR-22 may have considerable potential in identification of the prognosis and application of cancer therapy for HCC patients.

View Article: PubMed Central - PubMed

Affiliation: The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.

ABSTRACT

Background: Recently, microRNAs in cancer development have attracted much attention, but their roles in tumorigenesis are still largely unknown. In this study, a functional role of miR-22 in hepatocellular carcinoma (HCC) development has been identified.

Methods: Quantitative real-time PCR was used to determine the level of miR-22 transcript in HCC clinical samples, and its correlation with disease-free survival was determined using Kaplan-Meier method. Restoration of miR-22 expression was carried out in HCC cell lines to assess its influence on HCC cell proliferation and tumourigenicity.

Results: In the 160 paired HCC tissue samples, miR-22 expression was downregulated in HCC, and low miR-22 expression in HCC was predictive of poor survival in HCC patients. Functional studies indicated that ectopic expression of miR-22 significantly inhibits HCC cell proliferation and tumourigenicity. Furthermore, histone deacetylase 4 (HDAC4), known to have critical roles in cancer development, was proved to be directly targeted and regulated by miR-22. Furthermore, HDAC4 was upregulated in miR-22-downregulated HCC tissues, suggesting that downregulation of miR-22 might participate in HCC carcinogenesis and progression through potentiation of HDAC4 expression. In addition, cell proliferation was also suppressed by knockdown of HDAC4 or treatment with HDAC inhibitor trichostatin A in HCC cell lines.

Conclusion: miR-22, downregulated in HCC, has an anti-proliferative effect on HCC cells both in vitro and in vivo. Furthermore, miR-22 may have considerable potential in identification of the prognosis and application of cancer therapy for HCC patients.

Show MeSH
Related in: MedlinePlus