miR-107对卵巢癌细胞免疫逃逸的调控和紫杉醇耐药性的影响

doi:10.13481/j.1671-587X.20220323

Abstract

Abstract:

Objective： To investigate the effect of microRNA-107（miR-107）on the taxol （TAX）-resistance in the ovarian cancer cells by regulating immune escape through the mitogen-activated protein 3 kinase 7 （MAP3K7），and to charify its mechanism.

Methods

The 293T cells were divided into miR-NC group（transfected with miR-NC） and miR-107 mimics group（transfected with miR-107 mimics）.The ovarian cancer SKOV3 cells were treated with concentration gradient increasing method to obtain the TAX resistant SKOV3/TAX cells. The SKOV3/TAX cells were randomly divided into blank control group， TAX （given 4.0 μmol·L^－1 TAX） group， TAX+miR-107 mimics （given 4.0 μmol·L^－1 TAX and transfected with miR-107 mimics） group，TAX+miR-107 mimics+pcDNA-MAP3K7 （given 4.0 μ mol·L^－1 TAX and transfected with miR-107 mimics and pcDNA-MAP3K7）， and co-cultured with the human peripheral blood lymphocytes HPBL， respectively. Then they were divided into HPBL group， HPBL+SKOV3/TAX group， HPBL+ SKOV3/TAX+TAX group， HPBL + SKOV3/TAX+TAX+miR-107 mimics group and HPBL+ SKOV3/TAX+TAX+miR-107 mimics+pcDNA-MAP3K7 group. The expression levels of miR-107 in the cells in various groups were detected by real-time fluorescence quantitative PCR （RT-qPCR）method， the targeting relationship between miR-107 and MAP3K7 was verified by double luciferase reporter gene experiment， the expression levels of MAP3K7 and FAS proteins in the cells in various groups were detected by Western blotting method， the survival rates of the cells in various groups were detected by CCK-8 method， and the apoptotic rates of the cells in various groups were detected by flow cytometry.

Results

Compared with the human ovarian epithelial cells HOSEpic， the expression level of miR-107 in the ovarian cancer cells was decreased （P<0.05）. There was a targeted binding site between 3′-UTR of MAP3K7 and miR-107. The double luciferase reporter gene experiment results showed that compared with miR-NC group， the luciferase activity of wild-type MAP3K7 in miR-107 over-expression group was decreased （P<0.01）. The Western blotting results showed that the expression level of MAP3K7 protein in the cells in miR-107 over-expression group was significantly lower than that in miR-NC group （P<0.01）. The RT-qPCR results showed that compared with blank control group， the expression level of miR-107 mRNA in the SKOV3/TAX cells in TAX group was increased（P<0.01）； compared with TAX group， the expression level of miR-107 mRNA in the SKOV3/TAX cells in miR-107 MICs+TAX group was increased（P<0.05）. Compared with blank control group， the expression levels of MAP3K7 and FAS proteins in the SKOV3 / TAX cells in TAX group were decreased （P<0.01）； compared with TAX group， the expression levels of MAP3K7 and FAS proteins in the cells in TAX+miR-107 mimics SKOV3/TAX group were decreased （P<0.05 or P<0.01）； compared with TAX+miR-107 mimics group， the expression levels of MAP3K7 and FAS proteins in the SKOV3/TAX cells in TAX+miR-107 mimics+pcDNA-MAP3K7 group were increased（P<0.05 or P<0.01）.Compared with HPBL+SKOV3/TAX group， the expression level of FAS protein and apoptotic rate of the HPBL cells in HPBL+SKOV3/TAX+TAX group were decreased （P<0.05）； compared with HPBL+SKOV3/TAX+TAX group， the expression level of FAS protein and the apoptotic rate in the HPBL cells in HPBL+SKOV3/TAX+TAX + miR-107 mimics group were decreased（P<0.05）； compared with HPBL+SKOV3/TAX+TAX+miR-107 mimics group， the expression level of FAS protein in the HPBL cells in HPBL+SKOV3/TAX+TAX+miR-107 mimics+pcDNA-MAP3K7 group was decreased （P<0.01）， and the apoptotic rate was decreased （P<0.01）. Compared with blank control group， the survival rate of the SKOV3/TAX cells in TAX group was decreased （P<0.05）；compared with TAX group，the survival rate of the SKOV3/TAX cells in TAX+miR-107 mimics group was significantly decreased（P<0.05）. Compared with TAX + miR-107 mimics group， the survival rate of the SKOV3/TAX cells in TAX+miR-107 mimics+pcDNA-MAP3K7 group was increased （P<0.05）. The apoptotic rate of the SKOV3/TAX cells in TAX group was significantly higher than that in blank control group （P<0.05）， the apoptotic rate of the SKOV3/TAX cells in TAX+miR-107 group was significantly higher than that in TAX group （P<0.05）， and the apoptotic rate of the cells in TAX+miR-107 mimics+pcDNA-MAP3K7 group was lower than that in TAX+miR-107 mimics group （P<0.05）.

Conclusion

MiR-107 is low-expressed in the SKOV3/TAX cells， and over-expression of miR-107 could inhibit the immune escape of the SKOV3/TAX cells and alleviate the TAX resistance of the ovarian cancer cells by inhibiting the expression of MAP3K7.

Key words: Ovarian neoplasm, MicroRNA-107, Immune escape, Taxol, Drug resistance

CLC Number:

R737.31

Qinghui WANG,Bo LI,Chuancui HU,Mingchao NIE,Xiaomei ZHENG. Effects of miR-107 on regulation of immune escape and taxol resistance of ovarian cancer cells[J].Journal of Jilin University(Medicine Edition), 2022, 48(3): 734-743.

Figures/Tables 12

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References 28

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Group	Survival rate
TAX (μmol·L^－1)
0	99.21±0.48
1	84.29±2.78
2	65.07±3.54
3	52.86±3.09
4	44.93±3.29
5	32.52±3.11

Group	Expression level of miR-107 mRNA
Blank control	99.21±0.48
TAX	84.29±2.78^*
TAX+miR-107 mimics	65.07±3.54^△
TAX+miR-107 mimics+pcDNA-MAP3K7	52.86±3.09

Group	Expression level of MAP3K7	Expression level of FAS
Blank control	1.01±0.12	1.00±0.07
TAX	0.56±0.10^*	0.74±0.08^*
TAX+miR-107 mimics	0.25±0.07^△	0.30±0.06^△△
TAX+miR-107 mimics+pcDNA-MAP3K7	0.68±0.05^#	0.59±0.10^#

Group	Expression level of FAS	Apoptotic rate(η/%)
HPBL	1.02±0.11	6.24±1.77
HPBL+SKOV3/TAX	2.58±0.30^*	30.45±4.98^*
HPBL+SKOV3/TAX+TAX	1.95±0.19^△	20.33±2.95^△△
HPBL+SKOV3/TAX+TAX+miR-107 mimics	1.54±0.10^#	11.15±2.18^#
HPBL+SKOV3/TAX+TAX+miR-107 mimics+ pcDNA-MAP3K7	2.04±0.19^○	21.00±3.00^○

Group	Survival rate	Apoptotic rate
Blank control	1.95±0.22	11.01±2.17
TAX	1.56±0.08^*	17.43±1.68^**
TAX+miR-107 mimics	1.07±0.17^△	26.42±3.03^△
TAX+miR-107 mimics+pcDNA-MAP3K7	1.47±0.12^#	20.51±0.95^#

Effects of miR-107 on regulation of immune escape and taxol resistance of ovarian cancer cells

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