Regenerative Therapy (Mar 2023)
Cancer stem cell-like cells-derived exosomal lncRNA CDKN2B-AS1 promotes biological characteristics in thyroid cancer via miR-122-5p/P4HA1 axis
Abstract
Introduction: Here, the discussion focused on the function and possible mechanism of cancer stem cell-like cells (CSCs)-derived exosomal CDKN2B-AS1 in thyroid cancer. Methods: Specifically, the bioinformatics analysis, dual-luciferase reporter assay and RT-qPCR were conducted to obtain the expression and regulation of CDKN2B-AS1, and the downstream miR-122-5p/P4HA1 axis. Exosomes were identified by transmission electron microscopy. The uptake of exosome by recipient cells was observed by PKH67 labeling. Functional experiments and western blot were adopted to detect the effects of exosomal CDKN2B-AS1/miR-122-5p/P4HA1 axis on thyroid cancer cells. Tumor xenograft and in vivo metastasis model combined with RT-qPCR, western blot and hematoxylin-eosin staining verified the role of CDKN2B-AS1. Results: Exosomal CDKN2B-AS1 up-regulated P4HA1 expression through miR-122-5p. CDKN2B-AS1 and P4HA1 expressions were up-regulated, and miR-122-5p expression was down-regulated in thyroid cancer. Silent CDKN2B-AS1 reduced cell viability and stemness. CDKN2B-AS1 was found to be abundant in CSCs and CSCs-derived exosomes. Exosomal CDKN2B-AS1 silencing could transfer to thyroid cancer cells to elevate E-cadherin level, and diminish P4HA1, N-cadherin and Vimentin levels, thus impeding cell migration and invasion. MiR-122-5p inhibitor reversed the function of exosomal CDKN2B-AS1, while P4HA1 silencing attenuated the effect of miR-122-5p inhibitor. Exosomal CDKN2B-AS1 affected the growth and metastasis of thyroid cancer through the miR-122-5p/P4HA1 axis. Conclusion: CSCs-derived exosomal CDKN2B-AS1 acts as an oncogene in thyroid cancer through miR-122-5p/P4HA1 axis.
