Department of Gastrointestinal Surgery, Ruian People's Hospital, Ruian, Zhejiang, China.
Department of Pathology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Zhejiang, China.
Am J Physiol Gastrointest Liver Physiol. 2020 May 1;318(5):G841-G853. doi: 10.1152/ajpgi.00178.2019. Epub 2020 Mar 9.
Colorectal cancer (CRC) is one of the most common malignant tumors and is associated with a high mortality rate due to the lack of specific biomarkers available for early diagnosis, targeted therapies, and prognostic surveillance. In the present study, we investigated the function of and its underlying mechanism in CRC. Immunohistochemical staining and clinicopathological analysis were used to assess the expression of and its clinical significance in patients with CRC. Quantitative real-time polymerase chain reaction, cell proliferation, Western blot, wound healing, Transwell, and TOP/FOP flash reporter assays were used to investigate the function of and its underlying mechanism in CRC. expression was downregulated and negatively correlated with the depth of invasion, tumor size, metastasis, TNM stage, and epithelial-to-mesenchymal transition (EMT) markers in CRC specimens. negatively regulates the EMT, proliferation, invasion, migration, and the Wnt signaling pathway in vitro, as well as tumor growth and metastasis in vivo. Furthermore, activation of the Wnt signaling pathway by Wnt-3A negated the effect of overexpression, whereas inhibition of the Wnt signaling pathway by IWR-1 impaired the effect of the knockdown on the EMT. We concluded that downregulation is a common event in patients with CRC and is closely correlated with cancer progression and a poor prognosis. functions as a tumor suppressor in CRC, and its tumor suppressor function is mediated by negative regulation of the EMT through the Wnt signaling pathway. We investigate the function of and its underlying mechanism in colorectal cancer through quantitative real-time polymerase chain reaction, cell proliferation, Western blot, wound healing, Transwell, and TOP/FOP flash reporter assays. We conclude that can negatively regulate the epithelial-to-mesenchymal transition through the Wnt signaling pathway to inhibit the development of colorectal cancer.
结直肠癌（CRC）是最常见的恶性肿瘤之一，由于缺乏用于早期诊断、靶向治疗和预后监测的特异性生物标志物，其死亡率很高。本研究旨在探讨在 CRC 中作用及其潜在机制。采用免疫组织化学染色和临床病理分析评估在 CRC 患者中的表达及其临床意义。采用实时定量聚合酶链反应、细胞增殖、Western blot、划痕愈合、Transwell 侵袭和 TOP/FOP flash 报告基因检测等方法研究在 CRC 中的作用及其潜在机制。结果显示，在 CRC 标本中表达下调，与浸润深度、肿瘤大小、转移、TNM 分期和上皮间质转化（EMT）标志物呈负相关。在体外，负调控 EMT、增殖、侵袭、迁移和 Wnt 信号通路，以及体内肿瘤生长和转移。此外，Wnt-3A 激活 Wnt 信号通路可消除过表达的作用，而 Wnt 信号通路抑制剂 IWR-1 可削弱下调对 EMT 的影响。结论：CRC 患者中下调是一种常见事件，与癌症进展和预后不良密切相关。作为 CRC 的肿瘤抑制因子，其肿瘤抑制功能是通过 Wnt 信号通路负调控 EMT 介导的。通过实时定量聚合酶链反应、细胞增殖、Western blot、划痕愈合、Transwell 和 TOP/FOP flash 报告基因检测等方法研究在 CRC 中的作用及其潜在机制。结论：可以通过 Wnt 信号通路负调控上皮间质转化来抑制结直肠癌的发展。
