Department of General Surgery, Peking University First Hospital, Beijing, 100034, PR China.
Department of General Surgery, Peking University First Hospital, Beijing, 100034, PR China.
Exp Cell Res. 2020 Aug 1;393(1):112088. doi: 10.1016/j.yexcr.2020.112088. Epub 2020 May 12.
HMGA2 is associated with the regulation of cellular biological processes in various human disorders and cancer progression, yet little is known about how HMGA2 controls tumorigenesis. This study uncovered the mechanism of HMGA2-mediated regulation of tumorigenicity in pancreatic cancer. We showed that HMGA2 was highly expressed in pancreatic cancer cells and correlated with poor prognosis. HMGA2 expression knockdown inhibited the tumorigenicity of pancreatic cancer cells. Conversely, overexpression of HMGA2 promoted tumorigenicity. Combination of ChIP-Seq, RNA-Seq and dual-luciferase reporter assays revealed HMGA2 could directly regulate ANLN expression. Furthermore, we found ANLN could mediate the HMGA2-induced effects on pancreatic cancer cells. The identification of the regulatory mechanism of HMGA2 and ANLN will provide insights into the progression for human pancreatic cancer.
HMGA2 与多种人类疾病和癌症进展中的细胞生物学过程的调节有关，但关于 HMGA2 如何控制肿瘤发生的知之甚少。本研究揭示了 HMGA2 介导的胰腺癌肿瘤发生的调控机制。我们表明，HMGA2 在胰腺癌细胞中高度表达，并与不良预后相关。HMGA2 表达敲低抑制了胰腺癌细胞的致瘤性。相反，HMGA2 的过表达促进了致瘤性。ChIP-Seq、RNA-Seq 和双荧光素酶报告基因检测的组合表明，HMGA2 可以直接调节 ANLN 的表达。此外，我们发现 ANLN 可以介导 HMGA2 对胰腺癌细胞的诱导作用。HMGA2 和 ANLN 调控机制的确立将为人类胰腺癌的进展提供新的见解。
