AUTHOR=Shang Donghao , Liu Yuting , Chen Zhenghao 

TITLE=Exosome-Transmitted miR-128 Targets CCL18 to Inhibit the Proliferation and Metastasis of Urothelial Carcinoma

JOURNAL=Frontiers in Molecular Biosciences

VOLUME=8

YEAR=2022

URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2021.760748

DOI=10.3389/fmolb.2021.760748

ISSN=2296-889X

ABSTRACT=<p><bold>Objective:</bold> To investigate the regulatory function of exosome-transmitted <italic>miR-128</italic> and chemokine (C-C motif) ligand 18 (CCL18) on urothelial carcinomas (UCs).</p><p><bold>Methods:</bold> Tumor tissues, paracancerous tissues, and serum were collected from 20 patients with UCs (diagnosed at Beijing Friendship Hospital, Capital Medical University). CCL18 was detected by immunohistochemistry and ELISA. PCR was used to measure the expression levels of CCL18 and <italic>mir-183</italic>, <italic>miR-128</italic>, <italic>mir-33a</italic> in UCs. We acquired exosomes from mesenchymal stem cells and synthesized exosomes overexpressing <italic>miR-128</italic> (HMSC-128-EV). The effects of <italic>miR-128</italic> on the migration and invasion abilities, apoptosis and epithelial-mesenchymal transition of BUC T24 cells were investigated by co-culturing HMSC-128-EV. The therapeutic potential of <italic>miR-128</italic> on disease models was explored by injecting HMSC-128-EV into nude mice.</p><p><bold>Results:</bold> The expression of CCL18 in UCs was significantly higher than that in normal tissues (<italic>p</italic> &lt; 0.05), and the serum level of CCL18 in patients with UC was significantly increased compared with those in healthy controls (<italic>p</italic> &lt; 0.05). CCL18 overexpression or downregulation enhanced or suppressed the proliferation, migration and invasion of BUC T24 cells, resectively (<italic>p</italic> &lt; 0.05). The exosome-transmitted miR-128 can inhibit cell proliferation (<italic>p</italic> &lt; 0.05), invasion (<italic>p</italic> &lt; 0.05), and migration (<italic>p</italic> &lt; 0.05) in UCs, and these effects can be reversed by CCL18. In terms of apoptosis, <italic>miR-128</italic> was able to promote the occurrence of BUC T24 apoptosis (<italic>p</italic> &lt; 0.05), which can also be reversed by CCL18. In addition, <italic>miR-128</italic> can inhibit the proliferation (<italic>p</italic> &lt; 0.05) and metastasis (<italic>p</italic> &lt; 0.05) of UCs in nude mice.</p><p><bold>Conclusion:</bold> The <italic>miR-128</italic> inhibits the proliferation, invasion, migration of UCs, and promotes its apoptosis by regulating CCL18 secretion.</p>