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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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Inhibition of HDAC4 suppresses cell proliferation. Hep3B and SMMC7721 cells were transfected with control RNA or HDAC4 siRNA (A), or treated with TSA (100 n) (B) for the indicated time periods. Cell proliferation was measured using MTT assay. Data are shown as mean±s.d. (n=6). **P<0.01.
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fig7: Inhibition of HDAC4 suppresses cell proliferation. Hep3B and SMMC7721 cells were transfected with control RNA or HDAC4 siRNA (A), or treated with TSA (100 n) (B) for the indicated time periods. Cell proliferation was measured using MTT assay. Data are shown as mean±s.d. (n=6). **P<0.01.

Mentions: Next, we evaluated whether HCC cell growth is regulated by HDAC4 expression, which is targeted by miR-22. As shown in Figure 7, knockdown of HDAC4 or treatment with HDAC inhibitor trichostatin A (TSA) suppressed cell proliferation in HCC Hep3B and SMMC7721 cells. This result further suggests that miR-22 may suppress HCC cell proliferation at least partially through targeting HDAC4 expression.


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)

Inhibition of HDAC4 suppresses cell proliferation. Hep3B and SMMC7721 cells were transfected with control RNA or HDAC4 siRNA (A), or treated with TSA (100 n) (B) for the indicated time periods. Cell proliferation was measured using MTT assay. Data are shown as mean±s.d. (n=6). **P<0.01.
© Copyright Policy
Related In: Results  -  Collection

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

fig7: Inhibition of HDAC4 suppresses cell proliferation. Hep3B and SMMC7721 cells were transfected with control RNA or HDAC4 siRNA (A), or treated with TSA (100 n) (B) for the indicated time periods. Cell proliferation was measured using MTT assay. Data are shown as mean±s.d. (n=6). **P<0.01.
Mentions: Next, we evaluated whether HCC cell growth is regulated by HDAC4 expression, which is targeted by miR-22. As shown in Figure 7, knockdown of HDAC4 or treatment with HDAC inhibitor trichostatin A (TSA) suppressed cell proliferation in HCC Hep3B and SMMC7721 cells. This result further suggests that miR-22 may suppress HCC cell proliferation at least partially through targeting HDAC4 expression.

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