MALAT1 Is Associated with Poor Response to Oxaliplatin-Based Chemotherapy in Colorectal Cancer Patients and Promotes Chemoresistance through EZH2
Authors: Peilong Li
Haiyan Wang
Xin Zhang
Lutao Du
Tong Liu
Yongmei Yang
Chuanxin Wang
Lili Wang
Journal: Molecular Cancer Therapeutics (2017)
Discipline: CLINICAL MEDICINE
Keywords: oxaliplatin chemoresistance; colorectal cancer; epithelial-mesenchymal transition (EMT); long noncoding RNA (lncRNA); MALAT1
Affiliations: Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan, Shandong Province, China., Department of Clinical Laboratory, Women & Children's Hospital of Linyi, Linyi, Shandong Province, China., Department of Clinical Laboratory, The Second Hospital of Shandong University, Jinan, Shandong Province, China. .

Abstract:  A major reason for oxaliplatin chemoresistance in colorectal cancer is the acquisition of epithelial-mesenchymal transition (EMT) in cancer cells. The long noncoding RNA (lncRNA), 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 chemoresistance is not well known. In this study, we aim to investigate the prognostic and therapeutic role of lncRNA MALAT1 in colorectal cancer 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 colorectal cancer patients. Oxaliplatin-resistant colorectal cancer cells exhibited high MALAT1 expression and EMT. LncRNA MALAT1 knockdown enhances E-cadherin expression and inhibits oxaliplatin-induced EMT in colorectal cancer cells. EZH2 is highly expressed and associated with the 3' end region of lncRNA MALAT1 in colorectal cancer, and this association suppressed the expression of E-cadherin. 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 and leucovorin) treatment. In conclusion, this study illuminates the prognostic role of lncRNA MALAT1 in colorectal cancer patients receiving oxaliplatin-based treatment and further demonstrates how lncRNA MALAT1 confers a chemoresistant function in colorectal cancer. Thus, lncRNA MALAT1 may serve as a promising prognostic and therapeutic target for colorectal cancer patients. Mol Cancer Ther; 16(4); 739-51. ©2017 AACR. 

Retracted: No

PubPeer comments:
 Figure 2F and Figure 4C: Three cases where microscopy data have been duplicated and presented as something else. ![file] , 
 Figure 5G. * Green boxes: Two panels in the SW620 row appear to show an overlap. ![file] , 
 Retraction of Publication Mol Cancer Ther . 2021 Feb;20(2):451. doi: 10.1158 1535-7163.MCT-20-1028. Correction: MALAT1 is Associated with Poor Response to Oxaliplatin-based Chemotherapy in Colorectal Cancer Patients and Promotes Chemoresistance through EZH2 Peilong Li, Xin Zhang, Haiyan Wang, Lili Wang, Tong Liu, Lutao Du, Yongmei Yang, Chuanxin Wang PMID: 33547248 DOI: 10.1158 1535-7163.MCT-20-1028 Retraction of MALAT1 Is Associated with Poor Response to Oxaliplatin-Based Chemotherapy in Colorectal Cancer Patients and Promotes Chemoresistance through EZH2. Li P, Zhang X, Wang H, Wang L, Liu T, Du L, Yang Y, Wang C. Mol Cancer Ther. 2017 Apr;16(4):739-751. doi: 10.1158 1535-7163.MCT-16-0591. Epub 2017 Jan 9. PMID: 28069878 , 
 #3 Retraction retracted, corrected as a correction. [5 February 2021] : In the original version of this article (1), wrong images were used in Fig. 2F (invasion of si-NCu2013transfected HT29OxR cells), Fig. 4C (migration of HT29 cells), and Fig. 5G (si-EZH2u2013transfected SW620 cells). The error occurred when the authors arranged the images for these figures. The authors regret this error. , 
 It s apparently impossible to be retracted in an AACR journal. ,