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首页> 外文期刊>Experimental and therapeutic medicine >FSH stimulates expression of the embryonic gene HMGA2 by downregulating let-7 in normal fimbrial epithelial cells of ovarian high-grade serous carcinomas
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FSH stimulates expression of the embryonic gene HMGA2 by downregulating let-7 in normal fimbrial epithelial cells of ovarian high-grade serous carcinomas

机译：FSH通过下调let-7在卵巢高级浆液性癌的正常纤维上皮细胞中刺激胚胎基因HMGA2的表达

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摘要

FSH may increase the risk of ovarian malignancy and play a key role in ovarian carcinogenesis, although the mechanism(s) are undefined. HMGA2 overexpression has been observed to be an early genetic event in tumorigenesis. The present study was designed to investigate the effect of FSH on let-7, HMGA2 and p53 expression in normal fimbrial epithelial cells of ovarian high-grade serous carcinomas (HGSCs). A primary human Fallopian tube (FT) fimbrial epithelium ex vivo culture system of low-grade serous carcinomas (LGSCs) and HGSCs was established. The levels of HMGA2, let-7, p53 and FSHR were evaluated by western blotting and reverse transcription (RT)-PCR. Treatment with FSH significantly increased HMGA2 expression in a time-dependent manner and the let-7 expression levels decreased gradually over time in the normal fimbrial epithelial cells of HGSCs. However, we did not observe similar results in LGSCs. In addition, knockdown of let-7 suppressed HMGA2 expression. p53 was not detected in the normal fimbrial epithelial cells before or after FSH administration. Our results indicate that FSH increases the expression of HMGA2 by downregulating the expression of let-7 in normal fimbrial epithelial cells of HGSCs, but no occurrence of p53 mutation. The susceptibility of fimbria to FSH in HGSCs compared with those in LGSCs is different.
机译：FSH可能增加卵巢恶性肿瘤的风险，并在卵巢癌发生中起关键作用，尽管其机制尚不确定。 HMGA2过表达是肿瘤发生中的早期遗传事件。本研究旨在研究FSH对卵巢高级浆液性癌（HGSCs）正常纤维上皮细胞let-7，HMGA2和p53表达的影响。建立了低级浆液性癌（LGSCs）和HGSCs的人输卵管（FT）纤维上皮原代培养系统。 HMGA2，let-7，p53和FSHR的水平通过蛋白质印迹和逆转录（RT）-PCR进行评估。 FSH处理在HGSC的正常纤维上皮细胞中以时间依赖性方式显着增加了HMGA2的表达，而let-7的表达水平则随时间逐渐降低。但是，我们在LGSC中没有观察到类似的结果。另外，let-7的敲低抑制了HMGA2的表达。在FSH施用之前或之后，在正常的纤维上皮细胞中未检测到p53。我们的结果表明，FSH通过下调HGSC正常纤维上皮细胞let-7的表达来增加HMGA2的表达，但未发生p53突变。与LGSCs相比，HGSCs对FSH的菌毛敏感性不同。

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