A major reason for oxaliplatin chemoresistance in colorectal cancer (CRC) is the acquisition of epithelial-mesenchymal transition (EMT) in cancer cells. The long non-coding RNA, MALAT1, is a highly conserved nuclear ncRNA and a key regulator of metastasis development in several cancers. However, its role in oxaliplatin-induced metastasis and chemo-resistance is not well known. In this study, we aim to investigate the prognostic and therapeutic role of MALAT1 in CRC patients receiving oxaliplatin-based therapy, and further explore the potential transcriptional regulation through interaction with EZH2 based on the established HT29 oxaliplatin-resistant cells. Our results showed that high MALAT1 expression was associated with reduced patient survival and poor response to oxaliplatin-based chemotherapy in advanced CRC patients. Oxaliplatin-resistant CRC cells exhibited high MALAT1 expression and epithelial-mesenchymal transition (EMT). LncRNA MALAT1 knockdown enhances E-cadherin expression and inhibits oxaliplatin-induced EMT in CRC cells. EZH2 is highly expressed and associated with the 3' end region of lncRNA MALAT1 in CRC, and this association suppressed the expression of E-cadhrin. Furthermore, targeted inhibition of MALAT1 or EZH2 reversed EMT and chemoresistance induced by oxaliplatin. Finally, the interaction between lncRNA MALAT1 and miR-218 was observed, which further indicated its prognostic value in patients who received standard FOLFOX (oxaliplatin combine with 5-fluorouracil (5-FU) and leucovorin) treatment. In conclusion, this study illuminates the prognostic role of lncRNA MALAT1 in CRC patients receiving oxaliplatin-based treatment and further demonstrates how lncRNA MALAT1 confers a chemoresistant function in CRC. Thus, lncRNA MALAT1 may serve as a promising prognostic and therapeutic target for CRC patients.
- Received September 2, 2016.
- Revision received December 3, 2016.
- Accepted December 23, 2016.
- Copyright ©2017, American Association for Cancer Research.