Abstract
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.
Highlights
As one of the most common malignant cancers worldwide, colorectal cancer (CRC) has become the fifth leading cause of cancer death for men and women in China [1]
MiR-543 expression is downregulated in CRC tissues and inversely correlated with CRC metastasis miR-543 has been described as a tumor suppressor gene for breast cancer and endometrial cancer [14, 15] but as an oncogene for hepatocellular carcinoma [16]
The level of miR-543 was relatively lower in highly metastatic CRC cell lines than those in the four tumorigenic but low-metastatic cell lines (Figure 1D), indicating that miR-543 level is inversely correlated with the metastatic potential of CRC cell lines
Summary
As one of the most common malignant cancers worldwide, colorectal cancer (CRC) has become the fifth leading cause of cancer death for men and women in China [1]. A better understanding of the molecular mechanisms involved in CRC metastasis will provide diagnostic and prognostic markers and potential targets for the therapeutic intervention of CRC metastasis. It has been demonstrated that several key molecular events, including mutations in KRAS, aberrant activation of the Wnt and PI3K pathways and TP53 inactivation, are involved in the initiation and progression of CRC [6,7,8,9]. In addition to genetic aberrances, epigenetic alterations such as changes in microRNA (miRNA) deregulation and chromatin structure contribute to the development of CRC [10]. Great advances have been achieved in elucidating the specific roles of miRNAs in the initiation, progression and metastasis of CRC, the underlying mechanisms remain largely elusive [5, 10, 13]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
