近日，肿瘤学学术期刊《Oncotarget》杂志上在线发表了厦门大学生命科学学院欧阳高亮教授课题组在题为“microRNA-543 suppresses colorectal cancer growth and metastasis by targeting KRAS, MTA1 and HMGA2”的研究论文，论文揭示了miR-543调控结直肠癌生长和转移的机制。
microRNAs作为转录后调控的关键分子在众多和病理过程中行使重要功能。miR-543是一个与癌症相关的mircoRNA，但是它在结直肠癌发生发展中的功能并不清楚。欧阳高亮教授课题组研究发现，在APCmin/+自发形成结肠腺癌小鼠模型和AOM/DSS诱导的炎症相关肠癌模型的肿瘤组织中miR-543的表达水平呈现显著性降低。在结直肠癌病人的临床组织样本中miR-543的表达水平相对于正常的癌旁组织也有显著性下调，且这种下调与结直肠癌恶性程度和转移能力呈负相关。体外和体内实验表明，在结直肠癌细胞中过表达miR-543可明显抑制肿瘤细胞增殖、侵袭和转移。相反，抑制miR-543的表达则可增强结直肠癌细胞的增殖、侵袭和转移。通过在线数据库的筛选和体外实验的验证，该课题组进一步发现miR-543可通过直接靶向调控KRAS、MTA1和HMGA2来抑制结直肠癌的发生发展。这些研究表明miR-543在结直肠癌的生长和转移进程中发挥负调控作用。
原文摘要：
miR-543 has been implicated as having a critical role in the development of breast cancer, endometrial cancer and hepatocellular carcinoma. However, the exact clinical significance and biological functions of miR-543 in colorectal cancer (CRC) remain unclear. Here, we found that miR-543 expression significantly downregulated in tumors from patients with CRC, APCMin mice and a mouse model of colitis-associated colon cancer. miR-543 level was inversely correlated with the metastatic status of patients with CRC and the metastatic potential of CRC cell lines. Moreover, ectopic expression of miR-543 inhibited the proliferation and metastasis of CRC cells in vitro and in vivo by targeting KRAS, MTA1 and HMGA2. Conversely, miR-543 knockdown promoted the proliferation, migration and invasion of CRC cells in vitro and augmented tumor growth and metastasis in vivo. Furthermore, we found that miR-543 expression was negatively correlated with the levels of KRAS, MTA1 and HMGA2 in clinical samples. Collectively, these data show that miR-543 inhibits the proliferation and metastasis of CRC cells by targeting KRAS, MTA1 and HMGA2. Our study highlights a pivotal role for miR-543 as a suppressor in the regulation of CRC growth and metastasis and suggests that miR-543 may serve as a novel diagnostic and prognostic biomarker for CRC metastasis.
