Targeting CDK9: A novel biomarker in the treatment of endometrial cancer.

Targeting CDK9: A novel biomarker in the treatment of endometrial cancer.
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靶向 CDK9:治疗子宫内膜癌的新型生物标志物

DOI:
10.3892/or.2020.7746
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发表时间:
2020-11
期刊:
影响因子:
4.2
通讯作者:
Zhang T
Zhang T
中科院分区:
医学3区
文献类型:
--
作者:
He S;Fang X;Xia X;Hou T;Zhang T

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子宫内膜癌是女性生殖系统三大恶性肿瘤之一。虽然细胞周期蛋白依赖性激酶9(CDK 9)在各种类型的癌症中具有明确的致病作用,但关于其在子宫内膜癌中的功能知之甚少。我们的研究旨在评估CDK 9在子宫内膜癌中的表达和治疗潜力。通过免疫组化测定32例子宫内膜癌患者的原发性、转移性和复发性肿瘤组织中CDK 9的表达。采用小干扰RNA(siRNA)和CDK 9抑制剂检测CDK 9抑制剂对子宫内膜癌细胞抗凋亡活性和增殖的影响。采用集落形成实验和伤口愈合实验评价克隆形成和迁移能力。免疫组化结果显示,CDK 9在人子宫内膜癌细胞系中高度表达;此外,与患者匹配的原发性子宫内膜肿瘤组织相比,其在转移性和复发性子宫内膜肿瘤组织中升高。在子宫内膜癌中,用siRNA敲低CDK 9并用抑制剂抑制CDK 9活性可抑制细胞增殖并促进细胞凋亡。总之,我们的研究结果提供了证据表明,CDK 9可能是一个潜在的预后生物标志物,并在未来的子宫内膜癌的治疗有希望的治疗靶点。
Endometrial cancer is one of the three major malignant tumors of the female reproductive system. Although cyclin-dependent kinase 9 (CDK9) has a definitive pathogenic role in various types of cancer, little is known concerning its function in endometrial cancer. Our study was conducted to evaluate the expression and therapeutic potential of CDK9 in endometrial cancer. CDK9 expression was determined by immunohistochemistry in endometrial cancer tissues constructed with paired primary, metastatic, and recurrent tumor tissues from 32 endometrial cancer patients. Small interfering RNA (siRNA) and inhibitors of CDK9 were used to evaluate the effect of CDK9 inhibition on the anti-apoptotic activity and proliferation in endometrial cancer cells. Colony formation assay and wound-healing assays were adopted to assess clonal formation and migratory capacity. The results of the immunohistochemistry demonstrated that CDK9 was highly expressed in the human endometrial cancer cell lines; moreover, it was elevated in metastatic and recurrent endometrial tumor tissue compared when compared with that in patient-matched primary endometrial tumor tissue. Knockdown of CDK9 with siRNA and inhibition of CDK9 activity with the inhibitor suppressed cell proliferation and promoted apoptosis in endometrial cancer. In conclusion, our results provide evidence that CDK9 may be a potential prognostic biomarker and a promising therapeutic target for the treatment of endometrial cancer in the future.
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