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microRNA-34a as a Therapeutic Agent against Human Cancer.

Saito Y, Nakaoka T, Saito H - J Clin Med (2015)

Bottom Line: Cancer-related miRNAs are aberrantly expressed and act as tumor suppressors or oncogenes during carcinogenesis.Enforced expression of miR-34a induces cell cycle arrest, apoptosis, senescence, and suppression of epithelial-mesenchymal transition and inhibits cell proliferation of cancer stem cells.Epigenetic therapy with chromatin-modifying drugs such as inhibitors of DNA methylation and histone deacetylase has shown clinical promise for the treatment of malignancies.

View Article: PubMed Central - PubMed

Affiliation: Division of Pharmacotherapeutics, Keio University Faculty of Pharmacy, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan. saito-ys@pha.keio.ac.jp.

ABSTRACT
microRNAs (miRNAs) are small non-coding RNAs that down-regulate expression of various target genes. Cancer-related miRNAs are aberrantly expressed and act as tumor suppressors or oncogenes during carcinogenesis. We and other researchers have demonstrated that important tumor suppressor miRNAs are silenced by epigenetic alterations, resulting in the activation of target oncogenes in cancer cells. miR-34a was identified as a target of p53 and induces a G1 cell cycle arrest, senescence and apoptosis in response to DNA damage. miR-34a is an important tumor suppressor whose expression is epigenetically silenced in various human cancers. Enforced expression of miR-34a induces cell cycle arrest, apoptosis, senescence, and suppression of epithelial-mesenchymal transition and inhibits cell proliferation of cancer stem cells. Epigenetic therapy with chromatin-modifying drugs such as inhibitors of DNA methylation and histone deacetylase has shown clinical promise for the treatment of malignancies. Restoring of miR-34a expression by epigenetic therapy and/or delivery of miR-34a mimics may be a promising therapeutic strategy against human cancer.

No MeSH data available.


Related in: MedlinePlus

Biological effects of miR-34a in CSCs. The direct targets and biological effects of miR-34a in various CSCs are summarized; CSC; cancer stem cell.
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jcm-04-01951-f002: Biological effects of miR-34a in CSCs. The direct targets and biological effects of miR-34a in various CSCs are summarized; CSC; cancer stem cell.

Mentions: Since miR-34a suppresses many oncogenes and cancer stem cell markers including CD44, CDK4, CDK6, c-Met, Notch-1, Notch-2, SIRT1 and DLL1 as its target genes [11,19,20,21], miR-34a plays important roles in cancer stem cells. The direct targets and biological effects of miR-34a in various CSCs are summarized in Figure 2.


microRNA-34a as a Therapeutic Agent against Human Cancer.

Saito Y, Nakaoka T, Saito H - J Clin Med (2015)

Biological effects of miR-34a in CSCs. The direct targets and biological effects of miR-34a in various CSCs are summarized; CSC; cancer stem cell.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4663478&req=5

jcm-04-01951-f002: Biological effects of miR-34a in CSCs. The direct targets and biological effects of miR-34a in various CSCs are summarized; CSC; cancer stem cell.
Mentions: Since miR-34a suppresses many oncogenes and cancer stem cell markers including CD44, CDK4, CDK6, c-Met, Notch-1, Notch-2, SIRT1 and DLL1 as its target genes [11,19,20,21], miR-34a plays important roles in cancer stem cells. The direct targets and biological effects of miR-34a in various CSCs are summarized in Figure 2.

Bottom Line: Cancer-related miRNAs are aberrantly expressed and act as tumor suppressors or oncogenes during carcinogenesis.Enforced expression of miR-34a induces cell cycle arrest, apoptosis, senescence, and suppression of epithelial-mesenchymal transition and inhibits cell proliferation of cancer stem cells.Epigenetic therapy with chromatin-modifying drugs such as inhibitors of DNA methylation and histone deacetylase has shown clinical promise for the treatment of malignancies.

View Article: PubMed Central - PubMed

Affiliation: Division of Pharmacotherapeutics, Keio University Faculty of Pharmacy, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan. saito-ys@pha.keio.ac.jp.

ABSTRACT
microRNAs (miRNAs) are small non-coding RNAs that down-regulate expression of various target genes. Cancer-related miRNAs are aberrantly expressed and act as tumor suppressors or oncogenes during carcinogenesis. We and other researchers have demonstrated that important tumor suppressor miRNAs are silenced by epigenetic alterations, resulting in the activation of target oncogenes in cancer cells. miR-34a was identified as a target of p53 and induces a G1 cell cycle arrest, senescence and apoptosis in response to DNA damage. miR-34a is an important tumor suppressor whose expression is epigenetically silenced in various human cancers. Enforced expression of miR-34a induces cell cycle arrest, apoptosis, senescence, and suppression of epithelial-mesenchymal transition and inhibits cell proliferation of cancer stem cells. Epigenetic therapy with chromatin-modifying drugs such as inhibitors of DNA methylation and histone deacetylase has shown clinical promise for the treatment of malignancies. Restoring of miR-34a expression by epigenetic therapy and/or delivery of miR-34a mimics may be a promising therapeutic strategy against human cancer.

No MeSH data available.


Related in: MedlinePlus