MiR-492 is functionally involved in Oxaliplatin resistance in colon cancer cells LS174T via its regulating the expression of CD147

Abstract

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.

Evaluation of MCT1, MCT4 and CD147 Genes in Peripheral Blood Cells of Breast Cancer Patients and Their Potential Use as Diagnostic and Prognostic Markers

“…In fact, resistance to chemotherapy induced by MCT4 has been demonstrated: in a review, Bovenzi et al, 2015 [33] described 12 studies in which increased expression of MCT4 is associated with worse prognosis in patients with breast cancer, pancreatic, head and neck, hepatocellular carcinoma, gastric and colon. Drug-resistance mediated by CD147 was also described MCT4 by Peng et al, 2015 [34]. Thus, evaluation of expression after six months of chemotherapy can be a supplement for clinical onset of metastasis risk analysis.…”

MicroRNAs as potential therapeutic targets to predict responses to oxaliplatin in colorectal cancer: From basic evidence to therapeutic implication

“…Furthermore, lower levels of miR‐492 are associated with an increased expression of CD147 in an oxaliplatin‐resistant CRC cell line compared with its parental cell line. MiR‐492 increases the response to oxaliplatin treatment in xenograft CRC model by decreasing CD147 expression …”

“…MiR-492 increases the response to oxaliplatin treatment in xenograft CRC model by decreasing CD147 expression. 31 The overexpression of miR-199b in CRC cells is related to a dramatic upregulation of E-cadherin, as well as downregulation of vimentin and MMPs. MiR-199b directly targets SIRT1 and downregulates its expression and showed a significant increase in mesenchymal to epithelial transition.…”

MiR-505 mediates methotrexate resistance in colorectal cancer by targeting RASSF8

“…MiRNAs are short (19–25 nt long) non‐coding RNA molecules that modulate gene expression by transcriptional repression of mRNA . In various types of human cancers, miRNAs have been demonstrated to be involved in critical stages of cancer progression and the regulatory processes of gene expression, such as cell proliferation, apoptosis and migration, suggesting their potential oncogenic or tumour suppressive roles in cancer progression . Some previous studies have also substantiated that dysregulation of miRNA is correlated with cancer cell growth and metastasis.…”