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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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Related in: MedlinePlus

Endogenous miR-22 expression level in human normal liver. Data are shown as miRNA copies per 20 pg total RNA (equivalent of approximately one cell).
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fig1: Endogenous miR-22 expression level in human normal liver. Data are shown as miRNA copies per 20 pg total RNA (equivalent of approximately one cell).

Mentions: To investigate the roles of miR-22 in HCC development, we determined the expression level of miR-22 in human normal liver, as it was reported that a minimum threshold amounts must be reached for miRNAs to repress their target mRNAs (Brown et al, 2007; Sarasin-Filipowicz et al, 2009). In human distal normal liver tissue of liver hemangioma obtained from 10 patients during operation, we found that miR-22 was expressed at about 2 × 103 copies per 20 pg total RNA (Figure 1), equivalent of approximately one cell. Thus, the expression of miR-22 in human normal liver is much higher than the required amount of miRNA for targets repression, which is ∼100 copies per cell (Brown et al, 2007; Sarasin-Filipowicz et al, 2009).


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)

Endogenous miR-22 expression level in human normal liver. Data are shown as miRNA copies per 20 pg total RNA (equivalent of approximately one cell).
© Copyright Policy
Related In: Results  -  Collection

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

fig1: Endogenous miR-22 expression level in human normal liver. Data are shown as miRNA copies per 20 pg total RNA (equivalent of approximately one cell).
Mentions: To investigate the roles of miR-22 in HCC development, we determined the expression level of miR-22 in human normal liver, as it was reported that a minimum threshold amounts must be reached for miRNAs to repress their target mRNAs (Brown et al, 2007; Sarasin-Filipowicz et al, 2009). In human distal normal liver tissue of liver hemangioma obtained from 10 patients during operation, we found that miR-22 was expressed at about 2 × 103 copies per 20 pg total RNA (Figure 1), equivalent of approximately one cell. Thus, the expression of miR-22 in human normal liver is much higher than the required amount of miRNA for targets repression, which is ∼100 copies per cell (Brown et al, 2007; Sarasin-Filipowicz et al, 2009).

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