Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai, 200040, China.
Department of Surgery, Huashan Hospital, Fudan University, Shanghai, 200040, China.
Eur J Pharmacol. 2022 Feb 5;916:174727. doi: 10.1016/j.ejphar.2021.174727. Epub 2021 Dec 26.
The hepatocyte nuclear factor 4 gamma (HNF4G), a member of orphan nuclear receptors, is up-regulated and functions as an oncoprotein in a variety of tumors. Recent advances in understanding the biologic function and action mechanism of HNF4G in colorectal cancer (CRC) have not been fully elucidated. In the present study, we observed that HNF4G expression levels were significantly increased in CRC tissues compared with adjacent normal tissues, and HNF4G overexpression correlated with worse prognosis in colorectal cancer. Transfection with a small interference RNA (siRNA) targeting HNF4G in HCT116 and SW480 CRC cell lines significantly inhibited cell proliferation and promoted apoptosis in vitro. In contrast, overexpression of HNF4G increased cell proliferation and decreased the percentage of apoptotic cells. Moreover, we discovered that HNF4G was involved in CRC cell apoptosis via the caspase-dependent intrinsic pathway. Finally, knockdown of HNF4G expression led to attenuated colorectal cancer growth and promoted apoptosis in a xenograft mouse model. Collectively, these results indicate that HNF4G exerts as an oncogenic role in colorectal cancer and provides a potential therapeutic target.
肝细胞核因子 4 伽马（HNF4G）是孤儿核受体的成员，在多种肿瘤中上调并作为癌蛋白发挥作用。目前对 HNF4G 在结直肠癌（CRC）中的生物学功能和作用机制的理解尚未完全阐明。在本研究中，我们观察到 HNF4G 在 CRC 组织中的表达水平明显高于相邻正常组织，并且 HNF4G 的过表达与结直肠癌的预后不良相关。在 HCT116 和 SW480 CRC 细胞系中转染针对 HNF4G 的小干扰 RNA（siRNA）显著抑制了体外细胞增殖并促进了细胞凋亡。相反，HNF4G 的过表达增加了细胞增殖并降低了细胞凋亡的百分比。此外，我们发现 HNF4G 通过 caspase 依赖性内在途径参与 CRC 细胞凋亡。最后，敲低 HNF4G 的表达导致异种移植小鼠模型中的结直肠癌细胞生长减弱并促进了细胞凋亡。总之，这些结果表明 HNF4G 在结直肠癌中发挥致癌作用，并为潜在的治疗靶点提供了依据。
