The present study proposes a new direction to investigate the molecular mechanisms underlying the invasion and metastasis of CRC, whereby the interaction between MALAT1 and miR-20b-5p could be a novel therapeutic target for CRC.
Our study first revealed the novel roles of MALAT1 in promoting CRC metastasis through two mechanisms: first, MALAT1 binds miR-15 family members, to "de-inhibit" their effect on LRP6 expression, enhances β-catenin signaling, leading to elevated transcriptional levels of downstream target genes RUNX2.
The long non-coding RNA MALAT1 promotes epithelial-mesenchymal transition and angiogenesis in colorectal cancer, but it is unknown whether it affects the stemness of gastric cancer cells.
Collectively, we concluded that MALAT1 functioned as a ceRNA to promote colorectal cancer development and EZH2 expression through sponging miR-363-3p <i>in vitro</i> and <i>in vivo</i>.
These findings indicated that the YAP1-MALAT1-miR-126-5p axis could control angiogenesis and epithelial-mesenchymal transition in CRC, providing potential biomarkers and therapeutic targets for CRC.
Our data demonstrated that JMJD2C could enhance the metastatic abilities of CRC cells in vitro and in vivo by regulating the histone methylation level of MALAT1 promoter, thereby up-regulating the expression of MALAT1 and enhancing the activity of β-catenin signaling pathway, providing that JMJD2C might be a novel therapeutic target for CRC metastasis.
In particular, increased MALAT1 expression levels were significantly associated with decreased OS in patients with colorectal cancer (HR, 3.04; 95% CI, 1.77-4.31).
Finally, we investigated the clinical role of MALAT1 and found that high lncRNA MALAT1 expression level is associated with poor prognosis in CRC patients receiving oxymatrine treatment (P<0.01).
Taken together, our findings provided strong evidence for the hypothesis that genetic variants in lncRNA MALAT1 might contribute to the carcinogenesis of CRC.
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.
Recent studies have demonstrated that MALAT1 is involved in cancer metastasis and recurrence and it is up-regulated in cervical cancer, hepatocellular carcinoma, non-small cell lung cancer (NSCLC) and colorectal cancer.
Using MALAT1 lentiviral shRNA and over-expression constructs in CRC derived cell lines, LoVo and HCT116, we demonstrated that the anti-tumor effects of resveratrol on CRC are through inhibiting Wnt/β-catenin signaling, thus the expression of its target genes such as c-Myc, MMP-7, as well as the expression of MALAT1.