Center for Clinical Research and Translational Medicine, Yangpu Hospital, Tongji University School of Medicine, Shanghai 200090, China.
Institute of Gastrointestinal Surgery and Translational Medicine, Tongji University School of Medicine, Shanghai 200090, China.
Oxid Med Cell Longev. 2020 Dec 19;2020:5316276. doi: 10.1155/2020/5316276. eCollection 2020.
Colorectal cancer (CRC) is a leading cause of cancer-related death around the world whose recurrence and metastasis rate is high. Due to the underlying unclear pathogenesis, it is hard so far to predict the tumorigenesis and prevent its recurrence. YAP/TAZ has been reported to be activated and functioned as a potential oncogene in multiple cancer types and proved to be essential for the carcinogenesis of most solid tumors. In the present study, we found that YAP/TAZ was markedly upregulated in CRC tissues comparing with the adjacent noncancerous tissues due to the downregulation of LATS2, the main upstream regulator. We further identified miR-429 as a direct regulator of LATS2-YAP/TAZ activation, suggesting that the miR-429-LATS2-YAP/TAZ might be novel effective diagnostic axis and therapeutic targets for CRC.
结直肠癌(CRC)是全球癌症相关死亡的主要原因,其复发和转移率较高。由于潜在的发病机制不明确,迄今为止,很难预测肿瘤的发生并防止其复发。YAP/TAZ 已被报道在多种癌症类型中被激活并作为潜在的致癌基因发挥作用,并被证明对大多数实体肿瘤的癌变至关重要。在本研究中,我们发现由于主要上游调节剂 LATS2 的下调,YAP/TAZ 在 CRC 组织中明显上调,而在相邻的非癌组织中则明显下调。我们进一步鉴定出 miR-429 是 LATS2-YAP/TAZ 激活的直接调节剂,表明 miR-429-LATS2-YAP/TAZ 可能是 CRC 的新型有效诊断轴和治疗靶点。