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.
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.
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.
Taken together, these results indicate that miR-708 plays an important role in suppressing the development of CRC by directly targeting ZEB1 through AKT/mTOR signaling pathway, suggesting that miR-708 is a novel, effective therapeutic target for treating patients with CRC.
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).
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.
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.
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.
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.
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.
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.