Circular RNA CHST15 Sponges miR-155-5p and miR-194-5p to Promote the Immune Escape of Lung Cancer Cells Mediated by PD-L1

Abstract

BackgroundThe effects of up-regulated CircCHST15 on lung cancer remained unclear. In this study, the role of CircCHST15 in lung cancer was investigated.MethodsDual-luciferase reporter verified the bioinformatics prediction that CircCHST15 targeted miR-155-5p and miR-194-5p. The correlation between CircCHST15 and PD-L1 was analyzed by Pearson analysis. CCK-8 and colony formation was performed to determine the viability and proliferation of lung cancer cells. After the lung cancer (subcutaneous-xenotransplant) model was established in mice, the T cell subtype and related cytokines in mouse tumor tissues were detected by flow cytometry and ELISA. Moreover, the expressions of CircCHST15, miR-155-5p, miR-194-5p, immune-related, and proliferation-related factors of the lung cancer cells or mice tumor tissues were detected by immunohistochemistry, RT-qPCR, or Western blot.ResultsCircCHST15 and PD-L1 were high-expressed in lung cancer, and the two was positively correlated. CircCHST15 targeted miR-155-5p and miR-194-5p, the later further targeted PD-L1. Lung cancer cell viability and proliferation were increased by miR-155-5p and inhibited by miR-194-5p. CircCHST15 located in the cytoplasm promoted tumor growth, down-regulated the expressions of miR-155-5p and miR-194-5p, and up-regulated the expressions of PD-L1, Ki-67, PCNA, CCL17, CCL22, IFN-γ, TNF-β, and IL-10. Also, CircCHST15 decreased the CD8+ cells in mouse blood and tumor, but increased the Tregs in mouse tumor. PD-L1 inhibitor showed an opposite effect to CircCHST15 on mouse tumors.ConclusionCircCHST15 sponged miR-155-5p and miR-194-5p to promote the PD-L1-mediated immune escape of lung cancer cells.

microRNA-194 is increased in polycystic ovary syndrome granulosa cell and induce KGN cells apoptosis by direct targeting heparin-binding EGF-like growth factor

“…Previous studies have shown that miRNA is abnormally expressed in follicular fluid and has been shown to modulate follicular development in human GCs. miR-194 has been implicated in several different malignancies, such as gastric cancer cell growth and lung cancer cell apoptosis [ 38 , 39 ]. however, the role and effect of miR-194 in ovarian GCs are not entirely understood.…”

Role of Circular RNAs in the Regulation of Immune Cells in Response to Cancer Therapies

“…In addition, circCHST15 induces the production of both protumoral (TNF-β, and IL-10 and PD-L1) and antitumoral cytokines (IFN-γ and CCL17). The authors propose that increased expression of PD-L1 induces the inactivation CD8 + cells, leading to immune escape in lung cancer (Yang et al, 2021). In lung adenocarcinoma, circRNA-002178 increases PD-L1 expression, by acting as sponge of miR-34.…”

Circular RNA hsa_circ_0000190 Facilitates the Tumorigenesis and Immune Evasion by Upregulating the Expression of Soluble PD-L1 in Non-Small-Cell Lung Cancer

“…Multiple studies have demonstrated the role of circRNAs in regulating the expression of PD-L1 through the circRNA–miRNA–mRNA axis. CircCHST15 facilitated the PD-L1-mediated immune escape of lung cancer cells by inhibiting miR-155-5p and miR-194-5p [ 19 ]. The circ-CPA4–let-7 miRNA–PD-L1 axis regulated the growth of NSCLC cells and inhibited cytotoxic T cells in TIME [ 20 ].…”

“…Multiple studies have reported the role of circRNAs in regulating the expression of PD-L1 through circRNA–miRNA–mRNA axis. A number of circRNAs, such as circBART2.2, hsa_circ_0136666, circ-keratin 6c, CDR1-AS, circ-VIM, hsa_circ_0003288, CircCHST15, circ-CPA4, hsa-circRNA-002178, and Circ_0000284 were shown to affect PD-L1 expression, leading to tumor immune escape in various types of cancers, including nasopharyngeal carcinoma, colorectal cancer, esophageal cancer, hepatocellular carcinomas (HCC), and lung cancer [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ]. Our previous study discovered the correlation between hsa_circ_0000190 plasma level and PD-L1 level in patients with lung cancer.…”