Long noncoding RNA XIST expedites metastasis and modulates epithelial–mesenchymal transition in colorectal cancer

Abstract

Tumor progression and metastasis is the main cause of death in colorectal cancer (CRC). Long noncoding RNAs (lncRNAs) are critical regulators in various diseases including human cancer. In this study, we found that lncRNA XIST was overexpressed in CRC cell lines and tissues. High expression of lncRNA XIST was associated with adverse overall survival in CRC patients. Knockdown of lncRNA XIST remarkably inhibited CRC cell proliferation, invasion, epithelial–mesenchymal transition (EMT) and CRC stem cell formation in vitro as well as tumor growth and metastasis in vivo. Further study indicated that knockdown of lncRNA XIST markedly increased the expression of microRNA-200b-3p (miR-200b-3p) that has been found to be downregulated in CRC tissues and cell lines, and luciferase activity assay indicated that lncRNA XIST could bind directly with miR-200b-3p. Moreover, knockdown of lncRNA XIST significantly reduced the expression of ZEB1, which was the direct target of miR-200b-3p, and the tumor suppressive effects caused by knockdown of lncRNA XIST could be rescued by re-expression of ZEB1 in CRC cells. Overall, our study demonstrated how lncRNA XIST regulates CRC progression and metastasis by competing for miR-200b-3p to modulate the expression of ZEB1. lncRNA XIST may be used as a biomarker to predict prognosis in CRC patients.

Knockdown of Long Non-Coding RNA XIST Inhibited Doxorubicin Resistance in Colorectal Cancer by Upregulation of miR-124 and Downregulation of SGK1

“…Increasing studies revealed the oncogenic function of XIST in several tumors, such as gastric cancer [26], nasopharyngeal carcinoma [27], and hepatocellular carcinoma [28], through inducing cell proliferation, invasion and metastasis.. There have been documents reporting the carcinogenicity of XIST in CRC [10,11]. Moreover, a previous study demonstrated that XIST was significantly upregulated in 5FU-resistant CRC cells, and enforced expression of XIST inhibited 5FU-induced cell cytotoxicity in CRC cells [12].…”

“…Dysregulation of XIST has been reported in the genesis and development of multiple neoplasms, highlighting its prognostic and clinicopathological value in cancers [9]. Recent studies have documented that XIST expression was significantly increased in CRC tissues and cells, and functioned as an oncogene in human CRC through facilitating cell proliferation, migration, invasion and EMT [10,11]. Moreover, it was also reported that XIST was significantly upregulated in 5-fluorouracil (5FU)-resistant CRC cells, and enhanced XIST restrained 5FU-induced cytotoxicity in CRC cells by promoting the expression of thymidylate synthase [12].…”

Knockdown XIST alleviates LPS‐induced WI‐38 cell apoptosis and inflammation injury via targeting miR‐370‐3p/TLR4 in acute pneumonia

“…XIST has been demonstrated to play oncogenic function in multiple tumours. For example, XIST regulates colorectal cancer development and metastasis by the competition of miR‐200b‐3p to regulate ZEB1 expression . Meanwhile, XIST regulates the growth, invasion, and migration of bladder cancer by interacting with miR‐124 to target androgen receptor .…”

The lncRNA SCARNA2 mediates colorectal cancer chemoresistance through a conserved microRNA‐342‐3p target sequence

“…Dysregulation of lncRNAs has been confirmed involved in initiation and progression in several cancers including CRC. Recently, more and more lncRNAs have been reported to play critical roles in CRC; however, the roles of lncRNAs in CRC are remaining poorly defined (Chen, Chen, et al, , Chen, Lu, et al, ; Li et al, ). Here, we found that SCARNA2 was obviously upregulated in CRC tissues compared with the ANTs.…”