近日，腫瘤學學術(shù)期刊《Oncotarget》雜志上在線發(fā)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(diào)控結(jié)直腸癌生長和轉(zhuǎn)移的機制。
microRNAs作為轉(zhuǎn)錄后調(diào)控的關(guān)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(guān)的mircoRNA，但是它在結(jié)直腸癌發(fā)生發(fā)展中的功能并不清楚。歐陽高亮教授課題組研究發(fā)現(xiàn)，在APCmin/+自發(fā)形成結(jié)腸腺癌小鼠模型和AOM/DSS誘導的炎癥相關(guān)腸癌模型的腫瘤組織中miR-543的表達水平呈現(xiàn)顯著性降低。在結(jié)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(diào)，且這種下調(diào)與結(jié)直腸癌惡性程度和轉(zhuǎn)移能力呈負相關(guān)。體外和體內(nèi)實驗表明，在結(jié)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(zhuǎn)移。相反，抑制miR-543的表達則可增強結(jié)直腸癌細胞的增殖、侵襲和轉(zhuǎn)移。通過在線數(shù)據(jù)庫的篩選和體外實驗的驗證，該課題組進一步發(fā)現(xiàn)miR-543可通過直接靶向調(diào)控KRAS、MTA1和HMGA2來抑制結(jié)直腸癌的發(fā)生發(fā)展。這些研究表明miR-543在結(jié)直腸癌的生長和轉(zhuǎn)移進程中發(fā)揮負調(diào)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.
