近日，腫瘤學學術期刊《Oncotarget》雜志上在線發表了廈門大學生命科學學院歐陽高亮教授課題組在題為“microRNA-543 suppresses colorectal cancer growth and metastasis by targeting KRAS, MTA1 and HMGA2”的研究論文，論文揭示了miR-543調控結直腸癌生長和轉移的機制。
microRNAs作為轉錄后調控的關鍵分子在眾多和病理過程中行使重要功能。miR-543是一個與癌癥相關的mircoRNA，但是它在結直腸癌發生發展中的功能并不清楚。歐陽高亮教授課題組研究發現，在APCmin/+自發形成結腸腺癌小鼠模型和AOM/DSS誘導的炎癥相關腸癌模型的腫瘤組織中miR-543的表達水平呈現顯著性降低。在結直腸癌病人的臨床組織樣本中miR-543的表達水平相對于正常的癌旁組織也有顯著性下調，且這種下調與結直腸癌惡性程度和轉移能力呈負相關。體外和體內實驗表明，在結直腸癌細胞中過表達miR-543可明顯抑制腫瘤細胞增殖、侵襲和轉移。相反，抑制miR-543的表達則可增強結直腸癌細胞的增殖、侵襲和轉移。通過在線數據庫的篩選和體外實驗的驗證，該課題組進一步發現miR-543可通過直接靶向調控KRAS、MTA1和HMGA2來抑制結直腸癌的發生發展。這些研究表明miR-543在結直腸癌的生長和轉移進程中發揮負調控作用。
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.
