(4) This transient loss is not only due to proteolytic breakdown but to a down-regulated synthesis and linked to an epithelial-mesenchymal transition (EMT) in tumor cells, and, thereby, zinc-finger-enhancer protein 1 (ZEB1) is the crucial transcriptional repressor of BM components in CRCs.
However, ZEB1 is not expressed in the epithelium of hereditary forms of CRCs that carry wild-type APC and where β-catenin is excluded from the nucleus (Lynch syndrome).
Taken together, SIX1 overexpression is suggested to occur in carcinogenesis, and contribute to repression of CDH1 expression and promotion of EMT partly through repression of miR-200-family expression and activation of ZEB1 in CRC.
Taken together, our study demonstrated that miR-200c inhibits metastatic ability by targeting ZEB1 in colon cancer cells SW480/620 and suggested that modulation of miR-200c could serve as therapeutic tool for inhibiting metastasis in colorectal cancer.
Expression of several miR-200c target genes (ZEB1, ETS1 and FLT1) and EMT markers (E-cadherin and vimentin) in CRC cell lines and tissue specimens was validated.
Through multiple experimental approaches, colorectal carcinoma (CRC) cell lines and samples from human primary CRC and ZEB1 (-/-) mice were used to examine ZEB1-mediated regulation of uPA and PAI-1 at the protein, mRNA, and transcriptional level.
Loss of ZFP36 expression in colorectal cancer correlates to wnt/ ß-catenin activity and enhances epithelial-to-mesenchymal transition through upregulation of ZEB1, SOX9 and MACC1.
From subgroup analyses we observed ZEB1 was found to be significantly associated with poor overall survival for patients with pancreatic cancer, gastric cancer and colorectal cancer, while ZEB2 was found to be significantly associated with poor overall survival for patients with hepatocellular carcinoma and gastric cancer.
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.
Mechanism experiments including RNA Immunoprecipitation (RIP) assay and dual luciferase reporter assays verified that KCNQ1OT1 acted as a competing endogenous RNA (ceRNA) in CRC by sponging microRNA-217 (miR-217) to up-regulate the expression of zinc finger E-box binding homeobox 1 (ZEB1).
Overall, the present study indicated that HCP5 played a key regulator in CRC development and progression by targeting HCP5/miR-139-5p/ZEB1 axis, which may serve as a novel therapeutic target for CRC therapy.
Clinical analysis showed that m<sup>6</sup>A can regulate the expression of RP11, further, RP11 regulated Siah1-Fbxo45/Zeb1 was involved in the development of CRC.