Abstract. The mortality rates associated with colorectal cancer (CRC) are high due to metastasis. Epithelial-to-mesenchymal transition (EMT) is a key step in tumor metastasis. The aim of the present study was to investigate the function of microRNA-20a (miR-20a) in EMT. The expression of miR-20a was analyzed in CRC tissues and cell lines using the reverse transcription-quantitative polymerase chain reaction. Plasmids containing miR-20a short hairpin RNA and miR-20a mimics were transfected into SW620 and LS174T cell lines, respectively. Cell counting kit-8, Transwell ® and wound healing assays were performed to assess the effects of miR-20a on cell proliferation, invasion and migration. EMT markers and matrix metalloproteinases (MMPs) were identified using western blotting. The results showed that increased expression of miR-20a in CRC tissues was associated with tumor invasion and lymph node metastasis (P<0.05). Further experiments indicated that miR-20a-knockdown inhibited the proliferation, invasion and migration of CRC cells, upregulated the expression of vimentin and tissue inhibitor of metalloproteinases-2 (TIMP-2) and downregulated the expression of E-cadherin, MMP-2 and MMP-9. The opposite effects were observed in CRC cell lines overexpressing miR-20a. In conclusion, these results have shown that the upregulation of miR-20a suppresses TIMP-2 expression, which subsequently increases the expression of MMP-2 and MMP-9, thereby promoting the EMT of CRC cells. These findings suggest that miR-20a represents a potential therapeutic target for patients with CRC.

The liver transplant (LT) situation represents an attractive model for studying hepatocellular carcinoma (HCC) metastasis. Based on microarray data, we previously found that miR-126 expression was lower in tumor tissues of patients with post-LT HCC recurrence compared with non-recurrence. In this study, we examined the expression of miR-126 in HCC samples from 68 patients who had undergone LT using quantitative real-time PCR and analyzed its correlation with clinicopathological features and prognosis of patients. Furthermore, we performed experimental analyses to explore the involvement of miR-126 in HCC metastasis. We found that miR-126 levels were lower in tumor tissues of patients with post-LT HCC recurrence in comparison to patients with no-recurrence (p = 0.009). Lower expression of miR-126 in HCC was associated significantly with tumor recurrence (p = 0.011) and poor survival (p = 0.009) of patients. Functional studies indicated that ectopic expression of miR-126 significantly inhibits HCC cells migration, invasion, proliferation and colony formation in vitro, and suppresses experimental lung colonization in vivo. Our study revealed that down-regulation of miR-126 plays an important role in HCC metastasis, and suggest a potential application of miR-126 in prognosis prediction and HCC treatment.

Chemotherapy remains the core of anticancer treatment. However, despite the tremendous strides made in the development of targeted anticancer therapies, emergence of resistance to chemotherapeutic drugs is still a major obstacle in the successful management of resistant tumors. Therefore, profound investigation into the in-depth molecular mechanisms of drug resistance is essential and may hopefully translate into effective therapies that can flip the switch from drug resistance to susceptibility. To develop novel-targeted therapy holds promise for conquering chemotherapy resistance, one of the major hurdles in current colon cancer treatment. Previous studies indicate that CD147 is involved in the progression of chemotherapy resistance in breast cancer and ovarian cancer cells and its expression is negative regulated by miR-492 in muscles cells. In the present study, we found that lower level of miR-492 is accompanied with increased expression of CD147 in Oxaliplatin-resistant colon cancer cell line LS174T/L-OHP as compared with its parental cell line LS174T. Exogenous expression of miR-492 in LS174T/L-OHP could sensitize its reaction on the treatment of Oxaliplatin, which is coincided with its directly reducing the expression of CD147. Furthermore, we found that knockdown of CD147 in LS174T/L-OHP could also sensitize its reaction of the treatment with Oxaliplatin. Besides, intratumoral delivering of miR-492 could also restore Oxaliplatin treatment response in Oxaliplatin-resistant xenografts in vivo. These findings provide direct evidences that the miR-492/CD147 axis might play an essential role in the Oxaliplatin resistance of colon cancer cells, suggesting that the miR-492/CD147 signaling cohort could be served as a novel therapeutic target for the treatment of chemotherapy resistant in colon cancer.