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MicroRNA 1301 通过调控 EMT 和自噬抑制人卵巢癌细胞对顺铂的耐药性。

MicroRNA 1301 inhibits cisplatin resistance in human ovarian cancer cells by regulating EMT and autophagy.

机构信息

Department of Gynecology, Chifeng City Hospital, Chifeng City, Inner Mongolia, China.

出版信息

Eur Rev Med Pharmacol Sci. 2020 Feb;24(4):1688-1696. doi: 10.26355/eurrev_202002_20343.

Abstract

OBJECTIVE

Ovarian cancer is prone to chemoresistance, leading to poor outcomes in patients. MicroRNA 1301 plays a regulatory role in multiple tumors. However, whether microRNA 1301 regulates cisplatin resistance in ovarian cancer cells remains unclear.

MATERIALS AND METHODS

The ovarian cancer SKOV3 cell line and the human ovarian cancer cisplatin-resistant strain cell SKOV3/DDP were cultured in vitro and microRNA1301 expression was analyzed by Real time PCR. MicroRNA1301 mimics and microRNA 1301 were transfected into SKOV3/DDP, respectively followed by analysis of cell proliferation by MTT assay, cell invasion, expression of autophagy genes ATG5 and Beclin1 and EMT-related transcription factors Snail and Slug by Real time PCR, expression of NF-κB and E-cadherin and N-cadherin by Western blot.

RESULTS

MicroRNA 1301 expression was significantly increased in SKOV3/DDP cells compared with that in SKOV3 cells (p<0.05). MicroRNA1301 mimics transfection into SKOV3/DDP up-regulated microRNA1301 expression, promoted cell proliferation, and invasion, inhibited ATG5 and Beclin1 expression, and promoted Snail and Slug expression, decreased E-cadherin expression and increased N-cadherin and NF-κB expression, compared with the control group, the differences were statistically significant (p<0.05). MicroRNA1301 inhibitor transfection into SKOV3/DDP cells could down-regulate the expression of microRNA1301 and significantly reversed the above changes. Compared with the control group, differences were statistically significant (p<0.05).

CONCLUSIONS

Targeting microRNA1301 can inhibit the proliferation of cisplatin-resistant cells and the development of EMT in human ovarian cancer cells by inhibiting the NF-κB signaling pathway, thereby inhibiting the occurrence and development of drug-resistant ovarian cancer.

摘要

目的

卵巢癌易发生化疗耐药,导致患者预后不良。微小 RNA 1301 在多种肿瘤中发挥调控作用。然而,微小 RNA 1301 是否调节卵巢癌细胞顺铂耐药尚不清楚。

材料和方法

体外培养卵巢癌 SKOV3 细胞系和人卵巢癌顺铂耐药株细胞 SKOV3/DDP,实时 PCR 分析微小 RNA1301 表达。分别将微小 RNA1301 模拟物和微小 RNA 1301 转染至 SKOV3/DDP 中,MTT 法分析细胞增殖,实时 PCR 分析自噬基因 ATG5 和 Beclin1 及 EMT 相关转录因子 Snail 和 Slug 表达,Western blot 分析 NF-κB 和 E-cadherin、N-cadherin 表达。

结果

与 SKOV3 细胞相比,SKOV3/DDP 细胞中微小 RNA 1301 表达明显增加(p<0.05)。微小 RNA1301 模拟物转染至 SKOV3/DDP 中,上调微小 RNA1301 表达,促进细胞增殖和侵袭,抑制 ATG5 和 Beclin1 表达,促进 Snail 和 Slug 表达,降低 E-cadherin 表达,增加 N-cadherin 和 NF-κB 表达,与对照组相比,差异有统计学意义(p<0.05)。微小 RNA1301 抑制剂转染至 SKOV3/DDP 细胞可下调微小 RNA1301 表达,显著逆转上述变化。与对照组相比,差异有统计学意义(p<0.05)。

结论

靶向微小 RNA1301 可通过抑制 NF-κB 信号通路抑制人卵巢癌细胞顺铂耐药细胞增殖和 EMT 的发展,从而抑制耐药性卵巢癌的发生和发展。

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