Department of Surgery, Minhang Hospital, Fudan University, Shanghai, China.
Department of Anesthesiology, Minhang Hospital, Fudan University, Shanghai, China.
Biochem Biophys Res Commun. 2019 Sep 10;517(1):172-179. doi: 10.1016/j.bbrc.2019.07.038. Epub 2019 Jul 23.
Colorectal cancer (CRC) is a common malignancy globally causing significant cancer-related mortality. Recent studies have proposed p38gamma (p38γ) as a novel cyclin-dependent kinase (CDK)-like kinase, promoting tumorigenesis and cancer progression. The current study evaluates p38γ expression and potential role in CRC. In HT-29 cells and primary human colon cancer cells, shRNA-induced p38γ silencing or CRISPR/Cas9-mediated p38γ knockout inhibited cell growth, proliferation, and migration, and induced significant apoptosis. Conversely, ectopic overexpression of p38γ further promoted the growth, proliferation, and migration of HT-29 cells and primary colon cancer cells. Retinoblastoma (Rb) phosphorylation and cyclins (E1/A) expression were decreased by p38γ silencing or KO, but increased with p38γ overexpression. p38γ mRNA and protein levels are significantly upregulated in human colon cancer tissues, when compared to levels in surrounding colon epithelial tissues. These results demonstrate that overexpression of p38γ can promote human CRC cell progression, and identify p38γ as a novel therapeutic target.
结直肠癌（CRC）是一种常见的恶性肿瘤，在全球范围内导致了大量与癌症相关的死亡。最近的研究提出 p38γ（p38γ）是一种新型的细胞周期蛋白依赖性激酶（CDK）样激酶，促进肿瘤发生和癌症进展。本研究评估了 p38γ 的表达及其在 CRC 中的潜在作用。在 HT-29 细胞和原代人结肠癌细胞中，shRNA 诱导的 p38γ 沉默或 CRISPR/Cas9 介导的 p38γ 敲除抑制细胞生长、增殖和迁移，并诱导明显的细胞凋亡。相反，p38γ 的异位过表达进一步促进了 HT-29 细胞和原代结肠癌细胞的生长、增殖和迁移。p38γ 沉默或 KO 降低了视网膜母细胞瘤（Rb）磷酸化和细胞周期蛋白（E1/A）的表达，但 p38γ 的过表达增加了它们的表达。与周围结肠上皮组织相比，p38γ mRNA 和蛋白水平在人结肠癌细胞组织中显著上调。这些结果表明，p38γ 的过表达可以促进人 CRC 细胞的进展，并将 p38γ 鉴定为一种新的治疗靶点。
