Abstract
Although there are reports of miR-125b being dysregulated in colorectal cancer (CRC) and associated with CRC progression, little is known about its intrinsic regulatory mechanisms. Here we detected the expression of miR-125b in CRC tissues, subsequently investigated the effect of miR-125b on the proliferation, apoptosis, cell cycle and metastasis on CRC cells. Our results showed that the expression of miR-125b was significantly decreased in CRC tissues comparing to adjacent tissues. However, with the stimulation of Granulocyte colony-stimulating factor (G-CSF), which was highly expressed in CRC tissues, the expression of miR-125b could be improved. Analysis of patient samples revealed that miR-125b presented a clear association with poor differentiation, positive lymph node metastasis, and advanced TNM stage. Overexpression of miR-125b inhibited cell proliferation, triggered G2/M cell cycle arrest, induced subsequent apoptosis, and promoted cell migration and invasion. Moreover, luciferase reporter assays and western blot clarified that the myeloid cell leukemia 1 (MCL1) was a direct target of miR-125b. Thus overexpression of MCL1 attenuated the pro-metastasis function of miR-125b in CRC cell lines. In addition, the protein expression level of MCL1 was decreased in CRC tissues from patients with positive lymph node metastasis, which had high miR-125b expression. Collectively, our study suggested that miR-125b induced by G-CSF plays a promoting role in the metastasis of CRC by targeting MCL1, which may serve as a novel therapeutic target for CRC metastasis.
Highlights
Colorectal cancer (CRC) has become the third leading cause of cancer-related death worldwide [1]
Our study suggested that miR-125b induced by Granulocyte colony-stimulating factor (G-CSF) plays a promoting role in the metastasis of colorectal cancer (CRC) by targeting myeloid cell leukemia 1 (MCL1), which may serve as a novel therapeutic target for CRC metastasis
We found that miR-125b was significantly downregulated in CRC tissues from patients without lymph node metastasis while upregulated in those with lymph node metastasis
Summary
Colorectal cancer (CRC) has become the third leading cause of cancer-related death worldwide [1]. Despite advanced treatment modalities in recent decades, the 5-year survival rate of CRC remains unsatisfied [2] because approximately half of CRC patients develop metastases disease, especially liver metastases [3]. A better understanding of molecular mechanisms involved in the progression of CRC is crucial to explore novel therapeutic targets for CRC treatment. MiRNAs can function as tumor suppressors or oncogenes according to their targets [4]. Numerous miRNAs have been identified as important in CRC development, there is a limited application to clinical diagnosis and treatment [5]. Endless efforts are focused on the search of useful miRNAs as diagnosis markers and therapy targets for CRC patients
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