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miR-513a-3p 通过抑制 HOXB7 介导的 EMT 过程促进卵巢癌细胞对顺铂的敏感性。

MiR-513a-3p inhibits EMT mediated by HOXB7 and promotes sensitivity to cisplatin in ovarian cancer cells.

机构信息

Department of Gynecology and Obstetrics, Ningbo Zhenhai Lianhua Hospital, Ningbo, China.

出版信息

Eur Rev Med Pharmacol Sci. 2020 Oct;24(20):10391-10402. doi: 10.26355/eurrev_202010_23389.

Abstract

OBJECTIVE

Our aim was to investigate the biological function and mechanism of action of miR-513a-3p in ovarian cancer cells.

MATERIALS AND METHODS

In this study, qRT-PCR, Western blots, and immunohistochemistry experiments were among the methods used to examine the expression of miR-513a-3p, HOXB7, and related transcripts within ovarian cancer cells. An MTT assay was conducted to evaluate the viability of ovarian cancer cells in the presence of cisplatin. Transwell and wound-healing assays were performed to examine cell migration and invasion. Dual-Luciferase reporter assays were used to evaluate interactions among the aforementioned target genes. In vivo tumorigenesis experiments were conducted to verify biological effects of miR-513a-3p and HOXB7.

RESULTS

HOXB7 expression was relatively higher and MiR-513a-3p expression was relatively lower in ovarian cancer cells. Down-regulated expression of miR-513a-3p promoted cell movement via its ability to regulate epithelial-mesenchymal transition (EMT). Furthermore, decreased expression of miR-513a-3p resulted in increased sensitivity to cisplatin and resulted in poor prognosis in ovarian cancer patients who had relapsed after treatment with cisplatin. However, HOXB7 reversed the impact of miR-513a-3p in ovarian cancer cells. These results suggested that miR-513a-3p altered EMT mediated by HOXB7 and cisplatin-resistance.

CONCLUSIONS

MiR-513a-3p plays a critical role in promoting sensitivity to cisplatin and tumorigenesis via targeting HOXB7 in ovarian cancer.

摘要

目的

研究 miR-513a-3p 在卵巢癌细胞中的生物学功能和作用机制。

材料与方法

本研究采用 qRT-PCR、Western blot 和免疫组织化学实验等方法检测卵巢癌细胞中 miR-513a-3p、HOXB7 和相关转录物的表达。采用 MTT 法检测顺铂存在下卵巢癌细胞的活力。Transwell 和划痕愈合实验检测细胞迁移和侵袭。双荧光素酶报告实验评估上述靶基因之间的相互作用。体内肿瘤发生实验验证 miR-513a-3p 和 HOXB7 的生物学效应。

结果

HOXB7 在卵巢癌细胞中的表达相对较高,而 miR-513a-3p 的表达相对较低。miR-513a-3p 的下调表达通过调节上皮-间充质转化(EMT)促进细胞运动。此外,miR-513a-3p 的下调表达导致对顺铂的敏感性增加,并导致接受顺铂治疗后复发的卵巢癌患者预后不良。然而,HOXB7 逆转了 miR-513a-3p 在卵巢癌细胞中的作用。这些结果表明,miR-513a-3p 通过靶向 HOXB7 改变 EMT 和顺铂耐药性。

结论

miR-513a-3p 通过靶向 HOXB7 在卵巢癌中发挥关键作用,促进顺铂敏感性和肿瘤发生。

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