(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.
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.
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.
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.
Furthermore, bioinformatic analyses showed that miR551b expression levels were markedly downregulated in the advanced-stage CRC tissues compared to normal tissues, and ZEB1 was associated with the disease progression in CRC patients.
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).
Knockdown of ZEB1 in CRC cells inhibited 8-oxo-dG induction by oxidative stress (H<sub>2</sub>O<sub>2</sub>) and inflammatory cytokines (interleukin (IL)1β).
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.
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).
Mechanistic study revealed that hsa_circ_0001178 acted as a competing endogenous RNA (ceRNA) for miR- 382/587/616 to upregulate ZEB1 (a key trigger of epithelial-to-mesenchymal transition), thereby promoting CRC metastatic dissemination.
Our previous study has demonstrated that knockdown of Grainyhead-like 2(GRHL2) in colorectal cancer (CRC) cells inhibited cell proliferation by targeting ZEB1.
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.
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.
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.