AUTHOR=Xian Di , Niu Liangbo , Zeng Jie , Wang Lei
TITLE=LncRNA KCNQ1OT1 Secreted by Tumor Cell-Derived Exosomes Mediates Immune Escape in Colorectal Cancer by Regulating PD-L1 Ubiquitination via MiR-30a-5p/USP22
JOURNAL=Frontiers in Cell and Developmental Biology
VOLUME=9
YEAR=2021
URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.653808
DOI=10.3389/fcell.2021.653808
ISSN=2296-634X
ABSTRACT=Background: This study tried to explore the mechanism of long non-coding RNA (lncRNA) KCNQ1OT1 in tumor immune escape.
Methods: Gene Expression Omnibus (GEO) and microarray analysis were used to screen the differentially expressed lncRNA and microRNA (miRNA) in normal tissues and tumor tissues. Quantitative reverse transcription PCR (RT-qPCR) was used to quantify KCNQ1OT1, miR-30a-5p, ubiquitin-specific peptidase 22 (USP22), and programmed death-ligand 1 (PD-L1). The interactive relationship between KCNQ1OT1 and miR-30a-5p was verified using dual-luciferase reporter gene assay and ribonucleoprotein immunoprecipitation (RIP) assay. Cell Counting Kit (CCK)-8, clone formation, wound healing, and apoptosis are used to detect the occurrence of tumor cells after different treatments. Protein half-life and ubiquitination detection are used to study the influence of USP22 on PD-L1 ubiquitination. BALB/c mice and BALB/c nude mice are used to detect the effects of different treatments on tumor growth and immune escape in vivo.
Results: The expression of lncRNA KCNQ1OT1 in tumor tissues and tumor cell-derived exosomes was significantly increased. The tumor-promoting effect of lncRNA KCNQ1OT1 was through the autocrine effect of tumor cell-derived exosomes, which mediates the miR-30a-5p/USP22 pathway to regulate the ubiquitination of PD-L1 and inhibits CD8+ T-cell response, thereby promoting colorectal cancer development.
Conclusion: Tumor cell-derived exosomes’ KCNQ1OT1 could regulate PD-L1 ubiquitination through miR-30a-5p/USP22 to promote colorectal cancer immune escape.