PE-132 : MiR-23b-3p Suppresses Migration, Invasion and EMT by Downregulating CD44 in Hepatocellular Carcinoma
춘·추계 학술대회 (KASL)(2020)
摘要
Aims: Cancer stem cells (CSC) play a key role in cancer invasion and metastasis. Among CSCs, CD44 has known as important modulators of epithelial-mesenchymal transition (EMT) together with transforming growth factor beta1 (TGF-s1). EMT is epithelial cells lose their polarity and acquire mesenchymal cell migratory characteristics. miRNA could lead to either EMT through the regulation of various transcription factors. This study aimed to investigate the role of miR-23b-3p regulating the EMT, migration and invasion as well as CD44 expression in HCC cell lines.
Methods: We induced EMT by TGF-s1 treatment or inhibited EMT by TGF-s1 inhibitors. Also, miR-23b-3p mimic and inhibitor were transfected into HCC cell lines. The expression of EMT-related mRNA and protein were detected by quantitative real-time PCR and western blot. Also, EMT characteristics analyzed with cell migration and invasion.
Results: FACS analysis showed high expression of CD44 in two HCC cell lines with different levels of TGF-s1 expression. TGF-s1-negative SNU-354 cells were treated with TGF-s1 to induce the EMT and TGF-s1-positive SNU-368 cells were treated with TGF-s1 inhibitor to induce the MET. The expression of miR-23b-3p was down-regulated during the EMT and up-regulated during the MET. The Inhibition of miR-23b-3p in SNU-354 cells promoted EMT, cell migration and invasion. In contrast, overexpression of miR-23b-3p in SNU-368 cells suppressed EMT, cell migration and invasion. In addition, TGF-s1 stimulation after miR-23b-3p overexpression induced neither the mesenchymal phenotype nor cell migration. Also, CD44 is a target of miR-23b-3p. CD44 expression was increased in miR- 23b-3p inhibitor cells, whereas miR-23b-3p overexpression cells reduced expression of the CD44 in HCC cells.
Conclusions: Overexpression of miR-23b-3p suppressed EMT, cell migration and invasion by targeting CD44. The results suggest that miR-23b-3p may serve as specific biomarkers and therapeutic targets for HCC.
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关键词
hepatocellular carcinoma,cd44
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