Limits...
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 is underexpressed in GC tissues and cell lines(A) qRT–PCR analysis of miR-145 expression level in human GC tissues (20 paired gastric cancer and adjacent non-tumor tissues). (B) qRT–PCR analysis of miR-145 expression level in normal gastric mucosa and GC cells. All qRT-PCR results are expressed as mean ± SEM from at least three independent experiments. (*p < 0.05; **p < 0.01.)
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4480708&req=5

Figure 3: miR-145 is underexpressed in GC tissues and cell lines(A) qRT–PCR analysis of miR-145 expression level in human GC tissues (20 paired gastric cancer and adjacent non-tumor tissues). (B) qRT–PCR analysis of miR-145 expression level in normal gastric mucosa and GC cells. All qRT-PCR results are expressed as mean ± SEM from at least three independent experiments. (*p < 0.05; **p < 0.01.)

Mentions: In our previous miRNA microarray analysis, we found that miR-145 was reduced in GC tissues compared with normal gastric tissues [20]. To confirm and extend this finding, we examined the expression of miR-145 in 20 pairs of GC and normal tissues (Supplementary Table 1), and four human gastric cell lines including SGC-7901, AGS, BGC-823, MKN-45 and normal GES-1 by qRT-PCR. miR-145 was significantly downregulated in 15 of 20 (75%) cancer samples (Figure 3A). Additionally, all four gastric cancer cell lines showed > 50% reduction compared with normal cells (Figure 3B). miR-145 reduction suggests that it may act as a tumor suppressor in 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 is underexpressed in GC tissues and cell lines(A) qRT–PCR analysis of miR-145 expression level in human GC tissues (20 paired gastric cancer and adjacent non-tumor tissues). (B) qRT–PCR analysis of miR-145 expression level in normal gastric mucosa and GC cells. All qRT-PCR results are expressed as mean ± SEM from at least three independent experiments. (*p < 0.05; **p < 0.01.)
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: miR-145 is underexpressed in GC tissues and cell lines(A) qRT–PCR analysis of miR-145 expression level in human GC tissues (20 paired gastric cancer and adjacent non-tumor tissues). (B) qRT–PCR analysis of miR-145 expression level in normal gastric mucosa and GC cells. All qRT-PCR results are expressed as mean ± SEM from at least three independent experiments. (*p < 0.05; **p < 0.01.)
Mentions: In our previous miRNA microarray analysis, we found that miR-145 was reduced in GC tissues compared with normal gastric tissues [20]. To confirm and extend this finding, we examined the expression of miR-145 in 20 pairs of GC and normal tissues (Supplementary Table 1), and four human gastric cell lines including SGC-7901, AGS, BGC-823, MKN-45 and normal GES-1 by qRT-PCR. miR-145 was significantly downregulated in 15 of 20 (75%) cancer samples (Figure 3A). Additionally, all four gastric cancer cell lines showed > 50% reduction compared with normal cells (Figure 3B). miR-145 reduction suggests that it may act as a tumor suppressor in 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