| 张馨月,陈 亮,王 华.MiR-374a通过PTEN/AKT信号通路调节乳腺癌细胞的增殖和凋亡[J].肿瘤学杂志,2020,26(9):762-766. |
| MiR-374a通过PTEN/AKT信号通路调节乳腺癌细胞的增殖和凋亡 |
| MicroRNA-374a Regulates Proliferation and Apoptosis of Breast Cancer Cells via PTEN/AKT Signaling Pathway |
| 投稿时间：2019-09-03 |
| DOI：10.11735/j.issn.1671-170X.2020.09.B002 |
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| 中文关键词: 乳腺癌 miR-374a 增殖 凋亡 蛋白酪氨酸磷酸酶基因 |
| 英文关键词:breast cancer miR-374a proliferation apoptosis phosphatase and tensin homolog deleted on chromosome ten |
| 基金项目:江苏省第五期“333工程”科研资助项目（BRA2016187） |
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| 中文摘要: |
| 摘 要：［目的］ 探讨miR-374a在乳腺癌细胞增殖和凋亡中的作用，并进一步探讨其机制。［方法］ 采用实时荧光定量PCR（qRT-PCR）检测人乳腺癌细胞MCF-7及正常人乳腺细胞Hs 578Bst的miR-374a及PTEN mRNA转录水平，Western blot法测定MCF-7、Hs 578Bst组细胞及对照、 miR-374a抑制剂组细胞的PTEN、p-AKT蛋白表达变化，用CCK-8法及Tunel法分别观察对照组和miR-374a抑制剂组细胞的增殖和凋亡，并用Western blot法检测两组细胞的凋亡相关蛋白Bcl-2、Cleaved caspase-3、Cleaved caspase-9表达。［结果］ 与人正常乳腺Hs 578Bst细胞相比，乳腺癌MCF-7细胞的miR-374a表达水平显著性增高（P<0.001），PTEN mRNA及蛋白的表达水平显著性降低（P<0.001），而p-AKT蛋白表达水平明显升高（P<0.001）。miR-374a抑制剂可抑制乳腺癌细胞的增殖（P<0.001），并促进其凋亡的发生（P<0.001），降低抗凋亡蛋白Bcl-2表达水平（P<0.001）的同时活化凋亡相关蛋白Caspase-3和Caspase-9（P<0.001）。miR-374a 通过靶点PTEN影响AKT通路，miR-374a组细胞PTEN mRNA表达水平显著性降低（P<0.001），而miR-374a抑制剂处理后，PTEN蛋白水平显著性升高（P<0.001），p-AKT表达降低（P<0.001）。［结论］ miR-374a在乳腺癌细胞高表达，并通过调节PTEN/AKT信号通路抑制乳腺癌细胞的增殖，促进凋亡的发生。miR-374a/PTEN/AKT信号通路有望成为乳腺癌的新治疗靶点。 |
| 英文摘要: |
| Abstract：［Objective］ To investigate the effects of microRNA-374a(miR-374a) on the proliferation and apoptosis of breast cancer cells，and its mechanism.［Methods］ Real-time fluorescence quantitative polymerase chain reaction(qRT-PCR) was used to detect the transcript levels of miR-374a and phosphatase and tensin homolog deleted on chromosome ten(PTEN) in human breast cancer MCF-7 cells and normal human breast Hs 578Bst cells. The expression of miR-374a was inhibited by transfection with miR-374a inhibitor. Western blot method was used to detect the changes of PTEN，p-AKT，AKT protein expression in MCF-7 cells after transfection. CCK-8 and TUNEL methods were used to measure the cell proliferation and apoptosis，and the expressions of apoptosis-related proteins Bcl-2，cleaved caspase-3 and cleaved caspase-9 were detected by Western blot. ［Results］ Compared with Hs 578Bst cells，the expression of miR-374a in breast cancer MCF-7 cells significantly increased(P<0.001)，the expression of PTEN gene and protein significantly decreased(P<0.001)，and the protein expression level of p-AKT was significantly increased(P<0.001). The miR-374a inhibitor inhibited the proliferation of breast cancer cells(P<0.001) and promoted the cell apoptotic(P<0.001)，and decreased the expression of anti-apoptotic protein Bcl-2(P<0.001)，meanwhile activated apoptosis-related protein cleaved caspase-3 and cleaved caspase-9(P<0.001). Compared with control group，PTEN mRNA levels in MCF-7 cells were significantly down-regulated(P<0.001)，but when treated with miR-374a inhibitor，the protein level of PTEN was significantly up-regulated(P<0.001)，and p-AKT protein expression was significantly down-regulated(P<0.001). ［Conclusion］ The miR-374a is highly expressed in breast cancer cells，which promotes the proliferation of breast cancer cells and inhibits cell apoptosis by regulating PTEN/AKT signaling pathway. miR-374a/PTEN/AKT signaling pathway is expected to be a new therapeutic target for breast cancer. |
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