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The Effect of MicroRNA-124 Overexpression on Anti-Tumor Drug Sensitivity.

Chen SM, Chou WC, Hu LY, Hsiung CN, Chu HW, Huang YL, Hsu HM, Yu JC, Shen CY - PLoS ONE (2015)

Bottom Line: In the present study, we found that overexpression of miR-124 was associated with reduced DNA repair capacity in cultured cancer cells and increased sensitivity of cells to DNA-damaging anti-tumor drugs, specifically those that cause the formation of DNA strand-breaks (SBs).The translational relevance of this role of miR-124 in anti-tumor drug sensitivity is suggested by the finding that increased miR-124 expression correlates with better breast cancer prognosis, specifically in patients receiving chemotherapy.These findings suggest that miR-124 could potentially be used as a therapeutic agent to improve the efficacy of chemotherapy with DNA-damaging agents.

View Article: PubMed Central - PubMed

Affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.

ABSTRACT
MicroRNAs play critical roles in regulating various physiological processes, including growth and development. Previous studies have shown that microRNA-124 (miR-124) participates not only in regulation of early neurogenesis but also in suppression of tumorigenesis. In the present study, we found that overexpression of miR-124 was associated with reduced DNA repair capacity in cultured cancer cells and increased sensitivity of cells to DNA-damaging anti-tumor drugs, specifically those that cause the formation of DNA strand-breaks (SBs). We then examined which DNA repair-related genes, particularly the genes of SB repair, were regulated by miR-124. Two SB repair-related genes, encoding ATM interactor (ATMIN) and poly (ADP-ribose) polymerase 1 (PARP1), were strongly affected by miR-124 overexpression, by binding of miR-124 to the 3¢-untranslated region of their mRNAs. As a result, the capacity of cells to repair DNA SBs, such as those resulting from homologous recombination, was significantly reduced upon miR-124 overexpression. A particularly important therapeutic implication of this finding is that overexpression of miR-124 enhanced cell sensitivity to multiple DNA-damaging agents via ATMIN- and PARP1-mediated mechanisms. The translational relevance of this role of miR-124 in anti-tumor drug sensitivity is suggested by the finding that increased miR-124 expression correlates with better breast cancer prognosis, specifically in patients receiving chemotherapy. These findings suggest that miR-124 could potentially be used as a therapeutic agent to improve the efficacy of chemotherapy with DNA-damaging agents.

No MeSH data available.


Related in: MedlinePlus

Expression of miR-124 mRNA in breast cancer cell lines and U-2 OS (osteosarcoma) cells.MiR-124 expression level was determined by quantitative PCR and expressed as the fold change relative to RNU6B. Expression in the immortalized breast epithelial cell line, H184B5F5/M10, was used as the reference.
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pone.0128472.g001: Expression of miR-124 mRNA in breast cancer cell lines and U-2 OS (osteosarcoma) cells.MiR-124 expression level was determined by quantitative PCR and expressed as the fold change relative to RNU6B. Expression in the immortalized breast epithelial cell line, H184B5F5/M10, was used as the reference.

Mentions: To demonstrate the tumorigenic relevance of miR-124, we first examined miR-124 expression in eight breast cancer cell lines and an osteosarcoma cell line (U-2 OS) using stem-loop quantitative reverse transcription PCR. The levels of miR-124 in all nine lines were significantly reduced, to varying degrees, compared with H184B5F5/M10, an immortalized breast cell line (Fig 1). Notably, the triple-negative breast cancer cell line MB-MDA-231 had dramatically less expression of miR-124 than H184B5F5/M10.


The Effect of MicroRNA-124 Overexpression on Anti-Tumor Drug Sensitivity.

Chen SM, Chou WC, Hu LY, Hsiung CN, Chu HW, Huang YL, Hsu HM, Yu JC, Shen CY - PLoS ONE (2015)

Expression of miR-124 mRNA in breast cancer cell lines and U-2 OS (osteosarcoma) cells.MiR-124 expression level was determined by quantitative PCR and expressed as the fold change relative to RNU6B. Expression in the immortalized breast epithelial cell line, H184B5F5/M10, was used as the reference.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4482746&req=5

pone.0128472.g001: Expression of miR-124 mRNA in breast cancer cell lines and U-2 OS (osteosarcoma) cells.MiR-124 expression level was determined by quantitative PCR and expressed as the fold change relative to RNU6B. Expression in the immortalized breast epithelial cell line, H184B5F5/M10, was used as the reference.
Mentions: To demonstrate the tumorigenic relevance of miR-124, we first examined miR-124 expression in eight breast cancer cell lines and an osteosarcoma cell line (U-2 OS) using stem-loop quantitative reverse transcription PCR. The levels of miR-124 in all nine lines were significantly reduced, to varying degrees, compared with H184B5F5/M10, an immortalized breast cell line (Fig 1). Notably, the triple-negative breast cancer cell line MB-MDA-231 had dramatically less expression of miR-124 than H184B5F5/M10.

Bottom Line: In the present study, we found that overexpression of miR-124 was associated with reduced DNA repair capacity in cultured cancer cells and increased sensitivity of cells to DNA-damaging anti-tumor drugs, specifically those that cause the formation of DNA strand-breaks (SBs).The translational relevance of this role of miR-124 in anti-tumor drug sensitivity is suggested by the finding that increased miR-124 expression correlates with better breast cancer prognosis, specifically in patients receiving chemotherapy.These findings suggest that miR-124 could potentially be used as a therapeutic agent to improve the efficacy of chemotherapy with DNA-damaging agents.

View Article: PubMed Central - PubMed

Affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.

ABSTRACT
MicroRNAs play critical roles in regulating various physiological processes, including growth and development. Previous studies have shown that microRNA-124 (miR-124) participates not only in regulation of early neurogenesis but also in suppression of tumorigenesis. In the present study, we found that overexpression of miR-124 was associated with reduced DNA repair capacity in cultured cancer cells and increased sensitivity of cells to DNA-damaging anti-tumor drugs, specifically those that cause the formation of DNA strand-breaks (SBs). We then examined which DNA repair-related genes, particularly the genes of SB repair, were regulated by miR-124. Two SB repair-related genes, encoding ATM interactor (ATMIN) and poly (ADP-ribose) polymerase 1 (PARP1), were strongly affected by miR-124 overexpression, by binding of miR-124 to the 3¢-untranslated region of their mRNAs. As a result, the capacity of cells to repair DNA SBs, such as those resulting from homologous recombination, was significantly reduced upon miR-124 overexpression. A particularly important therapeutic implication of this finding is that overexpression of miR-124 enhanced cell sensitivity to multiple DNA-damaging agents via ATMIN- and PARP1-mediated mechanisms. The translational relevance of this role of miR-124 in anti-tumor drug sensitivity is suggested by the finding that increased miR-124 expression correlates with better breast cancer prognosis, specifically in patients receiving chemotherapy. These findings suggest that miR-124 could potentially be used as a therapeutic agent to improve the efficacy of chemotherapy with DNA-damaging agents.

No MeSH data available.


Related in: MedlinePlus