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转录因子 FoxM1 是 c-Myc 的下游靶点,有助于前列腺癌的发展。

Transcription factor FoxM1 is the downstream target of c-Myc and contributes to the development of prostate cancer.

机构信息

Department of Urology, Ningbo No.2 Hospital, No.41 Xibei Street, Ningbo, 315010, Zhejiang Province, People's Republic of China.

出版信息

World J Surg Oncol. 2018 Mar 20;16(1):59. doi: 10.1186/s12957-018-1352-3.

Abstract

BACKGROUND

Prostate cancer is a common malignancy and the second leading cause of cancer death in men. Elevated expression of the transcription factor FoxM1 and c-Myc has been identified in prostate cancer. However, the potential mechanism of elevated FoxM1 and c-Myc to the development of prostate cancer has not been identified.

METHODS

In this report, the mRNA level of FoxM1 and c-Myc was detected in 30 prostate cancer and para-cancer tissues. Then, we detected the expression level of FoxM1 by real-time PCR and Western blot after disturbance of the expression level of c-Myc in PC-3 cells. Whether c-Myc could bind to FoxM1 promoter was identified by ChIP assay. Finally, the migratory, invasive, and proliferative abilities in FoxM1 overexpressing and silencing PC-3 cells were detected by wound healing, transwell assay, CCK-8 assays, and Ki-67 protein level.

RESULTS

We found that the expression level of FoxM1 and c-Myc were both increased in prostate cancer samples compared with para-cancer samples. The expression level of FoxM1 was changed consistent with the protein level of c-Myc. ChIP assay detected the direct binding of c-Myc in FoxM1 gene promoter. Lastly, overexpression of FoxM1 increased the migratory, invasive, and proliferative abilities of PC-3 cells, and its downregulation significantly decreased the migratory, invasive, and proliferative abilities.

CONCLUSIONS

In conclusion, FoxM1 was significantly increased in prostate cancer samples, and it could regulate the proliferative and invasive ability of prostate cancer cells which might be a new target for prostate cancer. Besides, c-Myc could regulate the expression level of FoxM1 by directly binding to its gene promoter.

摘要

背景

前列腺癌是一种常见的恶性肿瘤,也是男性癌症死亡的第二大主要原因。在前列腺癌中已鉴定出转录因子 FoxM1 和 c-Myc 的表达升高。然而,升高的 FoxM1 和 c-Myc 对前列腺癌发展的潜在机制尚未确定。

方法

在本报告中,检测了 30 例前列腺癌和癌旁组织中的 FoxM1 和 c-Myc 的 mRNA 水平。然后,我们在 PC-3 细胞中干扰 c-Myc 的表达水平后,通过实时 PCR 和 Western blot 检测 FoxM1 的表达水平。通过 ChIP 测定鉴定 c-Myc 是否可以结合到 FoxM1 启动子上。最后,通过划痕愈合、Transwell 测定、CCK-8 测定和 Ki-67 蛋白水平检测 FoxM1 过表达和沉默 PC-3 细胞中的迁移、侵袭和增殖能力。

结果

我们发现与癌旁组织相比,前列腺癌样本中 FoxM1 和 c-Myc 的表达水平均升高。FoxM1 的表达水平与 c-Myc 的蛋白水平变化一致。ChIP 测定检测到 c-Myc 直接结合到 FoxM1 基因启动子上。最后,FoxM1 的过表达增加了 PC-3 细胞的迁移、侵袭和增殖能力,而下调其表达水平则显著降低了迁移、侵袭和增殖能力。

结论

总之,FoxM1 在前列腺癌样本中显著增加,它可以调节前列腺癌细胞的增殖和侵袭能力,这可能是前列腺癌的一个新靶点。此外,c-Myc 可以通过直接结合其基因启动子来调节 FoxM1 的表达水平。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3464/5859725/4110fa988e00/12957_2018_1352_Fig1_HTML.jpg

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