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Circular RNA circFGFR1 promotes progression and anti-PD-1 resistance by sponging miR-381-3p in non-small cell lung cancer cells.

ABSTRACT: BACKGROUND:Immune system evasion, distance tumor metastases, and increased cell proliferation are the main reasons for the progression of non-small cell lung cancer (NSCLC) and the death of NSCLC patients. Dysregulation of circular RNAs plays a critical role in the progression of NSCLC; therefore, further understanding the biological mechanisms of abnormally expressed circRNAs is critical to discovering novel, promising therapeutic targets for NSCLC treatment. METHODS:The expression of circular RNA fibroblast growth factor receptor 1 (circFGFR1) in NSCLC tissues, paired nontumor tissues, and cell lines was detected by RT-qPCR. The role of circFGFR1 in NSCLC progression was assessed both in vitro by CCK-8, clonal formation, wound healing, and Matrigel Transwell assays and in vivo by a subcutaneous tumor mouse assay. In vivo circRNA precipitation, RNA immunoprecipitation, and luciferase reporter assays were performed to explore the interaction between circFGFR1 and miR-381-3p. RESULTS:Here, we report that circFGFR1 is upregulated in NSCLC tissues, and circFGFR1 expression is associated with deleterious clinicopathological characteristics and poor prognoses for NSCLC patients. Forced circFGFR1 expression promoted the migration, invasion, proliferation, and immune evasion of NSCLC cells. Mechanistically, circFGFR1 could directly interact with miR-381-3p and subsequently act as a miRNA sponge to upregulate the expression of the miR-381-3p target gene C-X-C motif chemokine receptor 4 (CXCR4), which promoted NSCLC progression and resistance to anti-programmed cell death 1 (PD-1)- based therapy. CONCLUSION:Taken together, our results suggest the critical role of circFGFR1 in the proliferation, migration, invasion, and immune evasion abilities of NSCLC cells and provide a new perspective on circRNAs during NSCLC progression.

SUBMITTER: Zhang PF

PROVIDER: S-EPMC6900862 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Circular RNA circFGFR1 promotes progression and anti-PD-1 resistance by sponging miR-381-3p in non-small cell lung cancer cells.

Zhang Peng-Fei PF Pei Xu X Li Ke-Sang KS Jin Li-Na LN Wang Fei F Wu Jing J Zhang Xue-Mei XM

Molecular cancer 20191209 1

<h4>Background</h4>Immune system evasion, distance tumor metastases, and increased cell proliferation are the main reasons for the progression of non-small cell lung cancer (NSCLC) and the death of NSCLC patients. Dysregulation of circular RNAs plays a critical role in the progression of NSCLC; therefore, further understanding the biological mechanisms of abnormally expressed circRNAs is critical to discovering novel, promising therapeutic targets for NSCLC treatment.<h4>Methods</h4>The expressi ...[more]

PMID: 31815619

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Project description:As a recently discovered noncoding RNA, circular RNAs (circRNAs) have been identified to play key roles in cancer biology; however, the detailed functions and mechanisms of circRNAs in hepatocellular carcinoma (HCC) remain largely unclarified. RNA-seq analysis was used to screen the expression profiles of circRNAs in HCC. CircZNF566 expression in HCC tissues and cell lines was detected by qRT-PCR. In vitro CCK-8, colony formation, wound healing, transwell migration, and invasion assays and in vivo tumorigenesis and metastasis assays were conducted to determine the functions of circZNF566. Luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull-down assays were also performed to confirm the relationship between circZNF566 and miR-4738-3p. Bioinformatics analysis and luciferase reporter assays were employed to determine whether miR-4738-3p regulates tryptophan 2,3-dioxygenase (TDO2) expression. Finally, immunohistochemistry (IHC) was used to detect the level of TDO2 and determine its prognostic value. CircZNF566 was significantly upregulated in HCC tissues and cell lines. High circZNF566 expression in HCC tissues was positively correlated with clinicopathological features and poor prognosis. Functionally, in vitro experiments showed that circZNF566 promoted HCC cell migration, invasion, and proliferation, whereas in vivo experiments showed that circZNF566 promoted tumorigenesis and metastasis. Mechanistically, circZNF566 acted as a miR-4738-3p sponge to relieve the repressive effect of miR-4738-3p on its target TDO2. In addition, miR-4738-3p suppressed HCC cell migration, invasion, and proliferation, while TDO2 was positively correlated with pathological features and poor prognosis and promoted cell migration, invasion, and proliferation in HCC. CircZNF566 is a novel tumor promoter in HCC and functions through the circZNF566/ miR-4738-3p /TDO2 axis; in addition, circZNF566 may serve as a novel diagnostic marker, prognostic indicator, and target for the treatment of HCC.

Dataset Information

Circular RNA circFGFR1 promotes progression and anti-PD-1 resistance by sponging miR-381-3p in non-small cell lung cancer cells.

Publications

Circular RNA circFGFR1 promotes progression and anti-PD-1 resistance by sponging miR-381-3p in non-small cell lung cancer cells.

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