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miR-145 mediates the antiproliferative and gene regulatory effects of vitamin D3 by directly targeting E2F3 in gastric cancer cells.

Chang S, Gao L, Yang Y, Tong D, Guo B, Liu L, Li Z, Song T, Huang C - Oncotarget (2015)

Bottom Line: Inhibition of miR-145 reverses the antiproliferative effect of 1,25(OH)2D3.Furthermore, miR-145 expression was lower in tumors compared with matched normal samples and correlated with increased the E2F3 transcription factor protein staining.Altogether, our results indicate that miR-145 mediates the antiproliferative and gene regulatory effects of vitamin D3 in GC cells and might hold promise for prognosis and therapeutic strategies for GC treatment.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics and Molecular Biology/Key Laboratory of Environment and Genes Related to Diseases, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China.

ABSTRACT
VitaminD3 signaling is involved in inhibiting the development and progression of gastric cancer (GC), while the active vitamin D metabolite 1-alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3)-mediated gene regulatory mechanisms in GC remain unclear. We found that miR-145 is induced by 1,25(OH)2D3 in a dose- and vitamin D receptor (VDR)-dependent manner in GC cells. Inhibition of miR-145 reverses the antiproliferative effect of 1,25(OH)2D3. Furthermore, miR-145 expression was lower in tumors compared with matched normal samples and correlated with increased the E2F3 transcription factor protein staining. Overexpression of miR-145 inhibited colony formation, cell viability and induced cell arrest in S-phase in GC cells by targeting E2F3 and CDK6. miR-145 inhibition consistently abrogates the 1,25(OH)2D3-mediated suppression of E2F3, CDK6, CDK2 and CCNA2 genes. Altogether, our results indicate that miR-145 mediates the antiproliferative and gene regulatory effects of vitamin D3 in GC cells and might hold promise for prognosis and therapeutic strategies for GC treatment.

No MeSH data available.


Related in: MedlinePlus

miR-145-mediated calcitriol inhibited expression of cell cycle proteins(A) Western blot analyses in SGC-7901 cells after treatment of 1,25(OH)2D3 or transfection of miR-145 inhibitor. (B) Proposed model for miR-145 mediates the antiproliferative and gene regulatory effects of vitamin D3 by directly targeting E2F3 in GC cells.
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Figure 7: miR-145-mediated calcitriol inhibited expression of cell cycle proteins(A) Western blot analyses in SGC-7901 cells after treatment of 1,25(OH)2D3 or transfection of miR-145 inhibitor. (B) Proposed model for miR-145 mediates the antiproliferative and gene regulatory effects of vitamin D3 by directly targeting E2F3 in GC cells.

Mentions: In summary, we identified miR-145 as a novel target of 1,25(OH)2D3 in human GC. In addition, E2F3 and CDK6, the direct targets of miR-145, as well as their downstream cell cycle genes (CDK2 and CCNA2) are downregulated by 1,25(OH)2D3 (Figure 7A). Above all, we provide a novel evidence that 1,25(OH)2D3 inhibits cell proliferation in human cancer. miR-145, which presents multiple gene regulatory effects in human cancer, was identified as a direct target of 1,25(OH)2D3. Our results provide new insights on the vitamin D pathway in GC (Figure 7B). A further challenge will be to identify more targets of 1,25(OH)2D3 and to elucidate its inhibitory effects on GC.


miR-145 mediates the antiproliferative and gene regulatory effects of vitamin D3 by directly targeting E2F3 in gastric cancer cells.

Chang S, Gao L, Yang Y, Tong D, Guo B, Liu L, Li Z, Song T, Huang C - Oncotarget (2015)

miR-145-mediated calcitriol inhibited expression of cell cycle proteins(A) Western blot analyses in SGC-7901 cells after treatment of 1,25(OH)2D3 or transfection of miR-145 inhibitor. (B) Proposed model for miR-145 mediates the antiproliferative and gene regulatory effects of vitamin D3 by directly targeting E2F3 in GC cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4480708&req=5

Figure 7: miR-145-mediated calcitriol inhibited expression of cell cycle proteins(A) Western blot analyses in SGC-7901 cells after treatment of 1,25(OH)2D3 or transfection of miR-145 inhibitor. (B) Proposed model for miR-145 mediates the antiproliferative and gene regulatory effects of vitamin D3 by directly targeting E2F3 in GC cells.
Mentions: In summary, we identified miR-145 as a novel target of 1,25(OH)2D3 in human GC. In addition, E2F3 and CDK6, the direct targets of miR-145, as well as their downstream cell cycle genes (CDK2 and CCNA2) are downregulated by 1,25(OH)2D3 (Figure 7A). Above all, we provide a novel evidence that 1,25(OH)2D3 inhibits cell proliferation in human cancer. miR-145, which presents multiple gene regulatory effects in human cancer, was identified as a direct target of 1,25(OH)2D3. Our results provide new insights on the vitamin D pathway in GC (Figure 7B). A further challenge will be to identify more targets of 1,25(OH)2D3 and to elucidate its inhibitory effects on GC.

Bottom Line: Inhibition of miR-145 reverses the antiproliferative effect of 1,25(OH)2D3.Furthermore, miR-145 expression was lower in tumors compared with matched normal samples and correlated with increased the E2F3 transcription factor protein staining.Altogether, our results indicate that miR-145 mediates the antiproliferative and gene regulatory effects of vitamin D3 in GC cells and might hold promise for prognosis and therapeutic strategies for GC treatment.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics and Molecular Biology/Key Laboratory of Environment and Genes Related to Diseases, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China.

ABSTRACT
VitaminD3 signaling is involved in inhibiting the development and progression of gastric cancer (GC), while the active vitamin D metabolite 1-alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3)-mediated gene regulatory mechanisms in GC remain unclear. We found that miR-145 is induced by 1,25(OH)2D3 in a dose- and vitamin D receptor (VDR)-dependent manner in GC cells. Inhibition of miR-145 reverses the antiproliferative effect of 1,25(OH)2D3. Furthermore, miR-145 expression was lower in tumors compared with matched normal samples and correlated with increased the E2F3 transcription factor protein staining. Overexpression of miR-145 inhibited colony formation, cell viability and induced cell arrest in S-phase in GC cells by targeting E2F3 and CDK6. miR-145 inhibition consistently abrogates the 1,25(OH)2D3-mediated suppression of E2F3, CDK6, CDK2 and CCNA2 genes. Altogether, our results indicate that miR-145 mediates the antiproliferative and gene regulatory effects of vitamin D3 in GC cells and might hold promise for prognosis and therapeutic strategies for GC treatment.

No MeSH data available.


Related in: MedlinePlus