Icariin-Mediated miR-875-5p Inhibits Autophagy and Epithelial-Mesenchymal Transition by Regulation of MDM4 in Cervical Cancer

Abstract

MicroRNAs, one type of non-coding RNA, and Icariin have attracted tremendous attention concerning various diseases, especially cancers. Also, the function of Icariin on malignant behaviors by targeting miR-875-5p/MDM4 axis in cervical cancer remains unknown. MiR-875-5p analogs combined with MDM4 or Icariin were used to explore autophagy and epithelial-mesenchymal transition in cancer cells. Xenograft mice were highlighted to elucidate the influences of Icariin and miR-875-5p in vivo. As a result, miR-875-5p was cut down in cervical cancer cells, which promoted malignant phenotype, autophagy, and limited apoptosis in cervical cancer cells. Contrarily,miR-875-5p overexpression had a contrary performance in cervical cancer cells. miR-875-5p was validated as a sponge of MDM4. Enhanced expression of MDM4 weakened the performance of miR-875-5p mimic on autophagy and epithelial-mesenchymal transition. Moreover, Icariin reversed the stimulative action of the inhibitor on autophagy and xenograft tumor growth. Generally, These findings imply that Icariin could be identified as a curative avenue for cervical cancer via miR-875-5p/MDM4 axis.

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“…The study further revealed that icariin exerted its effects through the impairment of the TLR4/MyD88/NF-κB and Wnt/β-catenin pathways [147]. In another study, the role of icariin in modulating malignant behaviors by targeting the miR-875-5p/MDM4 axis in cervical cancer was investigated [148]. The study revealed downregulation of miR-875-5p in cervical cancer cells, promoting malignant phenotypes and autophagy and inhibiting apoptosis [148].…”

“…MiR-875-5p was identified as a sponge for MDM4, and elevated MDM4 expression attenuated the impact of miR-875-5p mimic on autophagy and epithelial-mesenchymal transition. However, icariin was found to counteract the inhibitory effects of miR-875-5p inhibitor on autophagy and xenograft tumor growth [148]. These suggest that ZINC000013380012 may serve as a promising lead molecule for the development of cervical cancer therapy, offering a potential alternative to current treatment modalities.…”

“…In another study, the role of icariin in modulating malignant behaviors by targeting the miR-875-5p/MDM4 axis in cervical cancer was investigated [148]. The study revealed downregulation of miR-875-5p in cervical cancer cells, promoting malignant phenotypes and autophagy and inhibiting apoptosis [148]. Conversely, the overexpression of miR-875-5p demonstrated opposing effects.…”