The Second Department of Comprehensive Medicine, Cancer Hospital of Huanxing Chaoyang District, Beijing, No. 1, Lujiaying South Lijia, Shibailidian Township, Chaoyang District, Beijing, 100023, China.
Appl Biochem Biotechnol. 2023 Nov;195(11):6913-6926. doi: 10.1007/s12010-023-04436-7. Epub 2023 Mar 23.
Cyclin-dependent kinase 12 (CDK12) has been found to regulate tumor progression. However, its function in gastric carcinoma (GC) remains controversial. This work aimed to explore the exact effect of CDK12 on GC progression. We detected the expression of CDK12 in GC cells and normal gastric mucosal epithelial cells. Then CDK12 function on GC cell proliferation, migration, and angiogenesis was researched by colony formation experiment, Transwell experiment, and angiogenesis assay. Moreover, CDK12 effect on the PI3K/AKT/mTOR pathway activity was explored by western blot. Further, we used LY294002 (10 μM) to treat GC cells to verify whether CDK12 regulates GC progression by activating the PI3K/AKT/mTOR pathway. Additionally, CDK12 effect on the expression of prognostic factors of GC was detected by western blot, including alkaline phosphatase (ALP) and Ki67. Quantitative real-time polymerase chain reaction and western blot were utilized to evaluate the expression of mRNAs and proteins. As a result, CDK12 was upregulated in GC cells. CDK12 overexpression facilitated the proliferation, migration, and angiogenesis of GC cells. However, CDK12 silencing showed an opposite result. CDK12 overexpression activated the PI3K/AKT/mTOR pathway, but CDK12 silencing inactivated it in GC cells. The blockage of the PI3K/AKT/mTOR pathway induced by LY294002 treatment counteracted the promotion of CDK12 on the proliferation, migration, and angiogenesis of GC. Further, CDK12 silencing suppressed the expression of ALP and Ki67 proteins in GC cells. Taken together, CDK12 promotes the proliferation, migration, and angiogenesis of GC by activating the PI3K/AKT/mTOR pathway. It may be a novel target for GC treatment.
周期蛋白依赖性激酶 12（CDK12）已被发现可调节肿瘤进展。然而，其在胃癌（GC）中的功能仍存在争议。本研究旨在探讨 CDK12 对 GC 进展的确切影响。我们检测了 GC 细胞和正常胃黏膜上皮细胞中 CDK12 的表达。然后通过集落形成实验、Transwell 实验和血管生成实验研究了 CDK12 对 GC 细胞增殖、迁移和血管生成的作用。此外，通过 Western blot 探讨了 CDK12 对 PI3K/AKT/mTOR 通路活性的影响。进一步，我们使用 LY294002（10 μM）处理 GC 细胞，以验证 CDK12 是否通过激活 PI3K/AKT/mTOR 通路来调节 GC 进展。此外，通过 Western blot 检测了 CDK12 对 GC 预后因素表达的影响，包括碱性磷酸酶（ALP）和 Ki67。定量实时聚合酶链反应和 Western blot 用于评估 mRNAs 和蛋白质的表达。结果显示，CDK12 在 GC 细胞中上调。CDK12 过表达促进了 GC 细胞的增殖、迁移和血管生成。然而，CDK12 沉默则表现出相反的结果。CDK12 过表达激活了 GC 细胞中的 PI3K/AKT/mTOR 通路，但 CDK12 沉默使其失活。LY294002 处理诱导的 PI3K/AKT/mTOR 通路阻断抵消了 CDK12 对 GC 细胞增殖、迁移和血管生成的促进作用。此外，CDK12 沉默抑制了 GC 细胞中 ALP 和 Ki67 蛋白的表达。综上所述，CDK12 通过激活 PI3K/AKT/mTOR 通路促进 GC 的增殖、迁移和血管生成。它可能成为 GC 治疗的新靶点。
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