<p>Curcumin Modifies Epithelial–Mesenchymal Transition in Colorectal Cancer Through Regulation of miR-200c/EPM5</p>

Abstract

Background: The serious side effect of current conventional treatments for patients with metastatic colorectal cancer (CRC) highlights the requirement of an alternative treatment strategy. Natural compounds, such as curcumin, have been gained much attention due to its low toxicity and anti-tumor effect. Methods: qPCR and Western blot were used to measure the molecular changes induced by curcumin. Wound-healing assay and transwell assay were conducted to study the effect on cell migration and invasion. RT 1 PCR array was performed to identify the miRNAs involved in curcumin-repressed EMT. Three algorithms and luciferase reporter assay were used to identify EPM5 as a target of miR-200c. The bioinformatical analysis of TCGA-COAD and other CRC cohorts were used to examine the association of EPM5 with EMT signatures and clinical relevance. The ectopic expression or siRNA-mediated knockdown of EPM5 was applied to study the role of EPM5 in CRC. Results: Treatment with curcumin changed the epithelial-mesenchymal transition (EMT)related gene expression, repressed cell migration and invasion in CRC cells. Its anti-tumor capability required the upregulation of miR-200c. EPM5 was a direct target of miR-200c and enriched in the consensus molecular subtype (CMS) 4 of CRC. Ectopic expression of EPM5 alone was sufficient to induce EMT in CRC. Downregulation of EPM5 was necessary for curcumin-repressed EMT, migration, and invasion. Higher expression of EPM5 was associated with the advanced TNM stages and poor survival in CRC. Conclusion: Our data provide the first evidence that the curcumin inhibits EMT in CRC by upregulation of miR-200c and downregulation of EPM5, and the use of curcumin might be able to prevent or delay CRC progression.

Curcumin inhibits the viability, migration and invasion of papillary thyroid cancer cells by regulating the miR‑301a‑3p/STAT3 axis

“…These observations indicated that curcumin inhibited EMT by upregulating miR-301a-3p expression. It has been reported that curcumin suppressed EMT through the miR-200c/EPM5 axis and the ERK5/AP-1 and TET1-NKD-Wnt signaling pathways ( 60-62 ). Furthermore, our results indicated that the targeting of STAT3 by miR-301a-3p and the overexpression of STAT3 also reversed the inhibitory effects of curcumin on EMT in TPC-1 cells.…”

Bioinformatics Analysis to Screen Key Targets of Curcumin against Colorectal Cancer and the Correlation with Tumor-Infiltrating Immune Cells

“…e high degree of malignancy, rapid development, poor prognosis, and chemoradiotherapy resistance of CRC often lead to the failure of treatment. Previous studies have shown that curcumin is a promising candidate for the treatment of CRC [15][16][17][18][19]. However, the regulatory mechanism of curcumin in CRC treatment has not been systematically elucidated.…”

“…Subsequent in vivo experiments confirmed that curcumin can reduce inflammation and CRC formation in mouse models [17]. Upregulation of miR-200c and downregulation of EPM5 can inhibit EMT in CRC to prevent or delay the progression of CRC [18]. It can also block G2/M and G1 cycles to inhibit cell growth and induce apoptosis of colorectal cancer cells [19].…”

MicroRNAs in Epithelial–Mesenchymal Transition Process of Cancer: Potential Targets for Chemotherapy

“…Further study displayed that miR-200c could directly target EPM5, and decreased EPM5 could contribute to curcumin-induced inhibition on EMT progression. Moreover, high expression of EPM5 was positively correlated with advanced TNM stages and poor survival in CRC patients [ 105 ]. Curcumin had anti-tumor effects and could up-regulate the expression of miR-206 in CRC cells.…”