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. 2017 May;37(5):2702-2710.
doi: 10.3892/or.2017.5537. Epub 2017 Mar 30.

Circulating microRNA-194 regulates human melanoma cells via PI3K/AKT/FoxO3a and p53/p21 signaling pathway

Ming Bai  1 , Mingzi Zhang  1 , Fei Long  1 , Nanze Yu  1 , Ang Zeng  1 , Ru Zhao  1
Affiliations

Circulating microRNA-194 regulates human melanoma cells via PI3K/AKT/FoxO3a and p53/p21 signaling pathway

Ming Bai et al. Oncol Rep. 2017 May.

Abstract

In the present study, we analyzed the role of microRNA-194 circulating regulated human melanoma cell growth. We found that microRNA-194 expression was markedly suppressed in human melanoma patients, compared with negative control group. Next, disease-free survival (DFS) and overall survival (OS) of high expression in human melanoma patients was higher than those of low expression in human melanoma patients. MicroRNA-194 overexpression inhibited cell proliferation, induced apoptosis, increased caspase-3/-9 activities and promoted Bax/Bcl-2 of human melanoma cells. Furthermore, microRNA-194 overexpression also suppressed PI3K/AKT/FoxO3a signaling pathway and induced p53/p21 signaling pathway. PI3K inhibitor, suppressed PI3K, phosphorylation-AKT, FoxO3a protein expression and increased the effects of microRNA-194 overexpression on cell growth, apoptosis, caspase-3/-9 activities and Bax/Bcl-2 protein expression of human melanoma cells through the induction of p53/p21 signaling pathway. Taken together, these data indicate that circulating microRNA-194 regulated human melanoma cells via PI3K/AKT/FoxO3a and p53/p21 signaling pathway.

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Figures

Figure 1.
Figure 1.
MicroRNA-194 expression of human melanoma patients.
Figure 2.
Figure 2.
Disease-free survival (DFS) and overall survival (OS) of human melanoma patients. (A) DFS and (B) OS of human melanoma patients.
Figure 3.
Figure 3.
MicroRNA-194 overexpression inhibits cell proliferation and induces apoptosis of human melanoma cells. MicroRNA-194 overexpression inhibited cell proliferation (A) and induced apoptosis (B) of human melanoma cells. Negative, negative control group; microRNA-194, microRNA-194 overexpression group; ##p<0.01 vs. negative control group.
Figure 4.
Figure 4.
MicroRNA-194 overexpression increases caspase-3/−9 activities of human melanoma cells. MicroRNA-194 overexpression increased caspase-3 (A) and caspase-9 activities (B) of human melanoma cells. Negative, negative control group; microRNA-194, microRNA-194 overexpression group; ##p<0.01 vs. negative control group.
Figure 5.
Figure 5.
MicroRNA-194 overexpression promotes Bax/Bcl-2 of human melanoma cells. MicroRNA-194 overexpression promoted Bax and Bcl-2 protein expression using western blot analysis (A) and Bax and Bcl-2 protein expression using statistical analysis (B) of human melanoma cells. Negative, negative control group; microRNA-194, microRNA-194 overexpression group; ##p<0.01 vs. negative control group.
Figure 6.
Figure 6.
MicroRNA-194 overexpression suppresses PI3K/AKT/FoxO3a signaling pathway of human melanoma cells. MicroRNA-194 overexpression promoted PI3K, p-AKT and FoxO3a protein expression using western blot analysis (A) and PI3K, p-AKT and FoxO3a protein expression using statistical analysis (B-D) of human melanoma cells. Negative, negative control group; microRNA-194, microRNA-194 overexpression group; ##p<0.01 vs. negative control group.
Figure 7.
Figure 7.
MicroRNA-194 overexpression induces p53/p21 signaling pathway of human melanoma cells. MicroRNA-194 overexpression promoted p53 and p21 protein expression using western blot analysis (A) and p53 and p21 protein expression using statistical analysis (B and C) of human melanoma cells. Negative, negative control group; microRNA-194, microRNA-194 overexpression group; ##p<0.01 vs. negative control group.
Figure 8.
Figure 8.
Suppression of PI3K affects microRNA-194 overexpression suppressed PI3K/AKT/FoxO3a signaling pathway of human melanoma cells. Suppression of PI3K affects microRNA-194 overexpression suppressed PI3K, p-AKT and FoxO3a protein expression using western blot analysis (A) and PI3K, p-AKT and FoxO3a protein expression using statistical analysis (B-D) of human melanoma cells. Negative, negative control group; microRNA-194, microRNA-194 overexpression group; PI3K inhibitor, PI3K inhibition group; ##p<0.01 vs. negative control group, ###p<0.01 vs. microRNA-194 overexpression group.
Figure 9.
Figure 9.
Suppression of PI3K affects microRNA-194 overexpression inhibited cell proliferation and induces apoptosis of human melanoma cells. Suppression of PI3K affects microRNA-194 overexpression inhibited cell proliferation (A) and induced apoptosis (B) of human melanoma cells. Negative, negative control group; microRNA-194, microRNA-194 overexpression group; PI3K inhibitor, PI3K inhibition group; ##p<0.01 vs. negative control group, ###p<0.01 vs. microRNA-194 overexpression group.
Figure 10.
Figure 10.
Suppression of PI3K affects microRNA-194 overexpression increased caspase-3/−9 activities of human melanoma cells. Suppression of PI3K affects microRNA-194 overexpression increased caspase-3 (A) and −9 activities (B) of human melanoma cells. Negative, negative control group; microRNA-194, microRNA-194 overexpression group; PI3K inhibitor, PI3K inhibition group; ##p<0.01 vs. negative control group, ###p<0.01 vs. microRNA-194 overexpression group.
Figure 11.
Figure 11.
Suppression of PI3K affects microRNA-194 overexpression promoted Bax/Bcl-2 of human melanoma cells. Suppression of PI3K affects microRNA-194 overexpression suppressed Bax and Bcl-2 protein expression using western blot analysis (A) and Bax and Bcl-2 protein expression using statistical analysis (B) of human melanoma cells. Negative, negative control group; microRNA-194, microRNA-194 overexpression group; PI3K inhibitor, PI3K inhibition group; ##p<0.01 vs. negative control group, ###p<0.01 vs. microRNA-194 overexpression group.
Figure 12.
Figure 12.
Suppression of PI3K affects microRNA-194 overexpression induced p53/p21 signaling pathway of human melanoma cells. Suppression of PI3K affects microRNA-194 overexpression suppressed p53 and p21 protein expression using western blot analysis (A) and p53 and p21 protein expression using statistical analysis (B and C) of human melanoma cells. Negative, negative control group; microRNA-194, microRNA-194 overexpression group; PI3K inhibitor, PI3K inhibition group; ##p<0.01 vs. negative control group, ###p<0.01 vs. microRNA-194 overexpression group.
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