Guo Xiaohong, Yue Longtao, Li Min, Dai Ang, Sun Junying, Fang Lei, Zhao Hai, Sun Qing
Department of Pathology, The First Affiliated Hospital, Shandong First Medical University, Jinan, Shandong, China.
Shandong Qianfoshan Hospital, Jinan, Shandong, China.
Carcinogenesis. 2022 Oct 22;43(9):865-873. doi: 10.1093/carcin/bgac054.
Colorectal cancer (CRC) is the predominant cause of cancer-related death worldwide, because of the lack of effective therapeutic targets. Estrogen-related receptor gamma (ESRRG), which belongs to the family of nuclear receptors, functions as an important element regulating gene transcription. In our report, we identified ESRRG as a potential tumor suppressor. The decreased level of ESRRG was initially observed in CRC and was highly associated with a poor prognosis. ESRRG overexpression abrogated cell growth and metastasis in vitro and in vivo. Mechanistically, ESRRG repressed the epithelial-to-mesenchymal transition process and antagonized Wnt signaling by regulating β-catenin degradation. In addition, significant ESRRG hypermethylation was found in CRC and inversely correlated with its expression. Consistently, the expression of ESRRG was induced after treatment with DNA demethylating agent 5-aza-2'-deoxycytidine. Taken together, these findings define a tumor-suppressive role of ESRRG in CRC, providing a potential novel therapeutic approach for this cancer.
由于缺乏有效的治疗靶点，结直肠癌（CRC）是全球癌症相关死亡的主要原因。雌激素相关受体γ（ESRRG）属于核受体家族，是调节基因转录的重要元件。在我们的报告中，我们将ESRRG鉴定为一种潜在的肿瘤抑制因子。最初在结直肠癌中观察到ESRRG水平降低，且与预后不良高度相关。ESRRG过表达在体外和体内均消除了细胞生长和转移。从机制上讲，ESRRG通过调节β-连环蛋白降解来抑制上皮-间质转化过程并拮抗Wnt信号。此外，在结直肠癌中发现了明显的ESRRG高甲基化，且与其表达呈负相关。一致地，用DNA去甲基化剂5-氮杂-2'-脱氧胞苷处理后，ESRRG的表达被诱导。综上所述，这些发现确定了ESRRG在结直肠癌中的肿瘤抑制作用，为这种癌症提供了一种潜在的新型治疗方法。
