Department of Gynecology and Obstetrics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, China.
J Immunol Res. 2021 Feb 11;2021:6645885. doi: 10.1155/2021/6645885. eCollection 2021.
Cervical cancer (CC) is a commonly diagnosed and primary consideration of cancer patient death in female reproductive system malignancy. Cyclin-dependent kinase 12 (CDK12), as a transcription-associated CDK, plays important roles in tumor-promoting behaviors, whereas the underlying mechanisms of in CC progression are still obscure. In this report, we investigated the role of in cervical cancer. The current study identified mRNA and protein expression remarkably upregulated in CC patients. Upregulated was closely associated with CC progression and poor prognosis. and functional experiments showed that knockdown of inhibited cancer cell proliferation and colony formation and promoted apoptosis. Further investigations demonstrated that regulated the immune microenvironment to facilitate the progression of CC cells by promoting macrophage infiltration. Meanwhile, we first demonstrated that nuclear import of CDK12 is mediated by TNPO1 and might be a new therapeutic target in oncology. Collectively, this study pointed out the potential of to serve as a novel therapeutic target in restricting CC proliferation and cell cycle process through promoting macrophage infiltration.
宫颈癌（CC）是女性生殖系统恶性肿瘤中常见的癌症患者死亡原因。细胞周期蛋白依赖性激酶 12（CDK12）作为一种转录相关的 CDK，在促进肿瘤的行为中发挥重要作用，而其在 CC 进展中的潜在机制仍不清楚。在本报告中，我们研究了在宫颈癌中的作用。本研究发现，在宫颈癌患者中显著上调了 mRNA 和蛋白表达。上调与 CC 的进展和预后不良密切相关。和功能实验表明，下调可抑制癌细胞增殖和集落形成，促进细胞凋亡。进一步的研究表明，通过促进巨噬细胞浸润来调节免疫微环境，从而促进 CC 细胞的进展。同时，我们首次证明 CDK12 的核输入是由 TNPO1 介导的，可能是肿瘤学中的一个新的治疗靶点。总之，这项研究指出，通过促进巨噬细胞浸润，可能成为一种限制 CC 增殖和细胞周期过程的新的治疗靶点。
