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Updated: Sep 7, 2025
Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
Circ_0092012 knockdown restrains non-small cell lung cancer progression by inhibiting cell malignant phenotype and
Jin Yan1, Jian Zhu1, Xiaoli Zhu2
1Department of Respiratory and Critical Care Medicine, Binhai County People's Hospital, Yancheng, Jiangsu, China.
Abstract:
Circular RNAs have been reported to play roles in non-small cell lung cancer (NSCLC) progression. Herein, this work aimed to investigate the potential value of circ_0092012 in NSCLC progression. Levels of genes and proteins were detected using quantitative reverse transcription-polymerase chain reaction and Western blot, respectively. The growth, malignant phenotypes and immune escape in NSCLC were investigated. The binding between microRNA (miR)-635 and circ_0092012 or programmed death ligand 1 (PDL1) was verified. Circ_0092012 was highly expressed in NSCLC. Circ_0092012 deficiency suppressed NSCLC cell proliferation, invasion and migration, moreover, as well as was able to inhibit the apoptosis of CD8 + T cells and induce higher interferon-γ and tumor necrosis factor-α levels when co-cultured with peripheral blood mononuclear cells. Mechanistically, circ_0092012 sponged miR-635, which targeted PDL1. Further rescue experiments suggested that the anticancer effects of circ_0092012 knockdown were reversed by miR-635 inhibition. Additionally, miR-635 re-expression suppressed NSCLC cell malignant phenotypes mentioned above and immune escape, which were attenuated by PDL1 overexpression. Moreover, circ_0092012 deletion retarded NSCLC growth in vivo. In all, circ_0092012 knockdown suppressed NSCLC cell oncogenic phenotypes and immune escape by miR-635/PDL1 axis.
Insights
Circular RNA circ_0092012 promotes non-small cell lung cancer (NSCLC) progression and immune escape. Knockdown of circ_0092012 inhibits NSCLC growth by regulating the miR-635/PDL1 axis.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Circular RNAs (circRNAs) are implicated in the progression of non-small cell lung cancer (NSCLC).
- The specific role of circ_0092012 in NSCLC remains largely unexplored.
Purpose of the Study:
- To investigate the functional role and underlying mechanism of circ_0092012 in NSCLC progression.
- To explore the potential of targeting circ_0092012 for NSCLC therapy.
Main Methods:
- Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot to detect gene and protein levels.
- Assessment of NSCLC cell proliferation, invasion, migration, and apoptosis.
- Investigation of immune cell responses (CD8+ T cells, PBMCs) and cytokine production (IFN-γ, TNF-α).
- Validation of interactions between microRNA (miR)-635, circ_0092012, and programmed death ligand 1 (PDL1).
- In vivo tumor growth assays in a mouse model.
Main Results:
- Circ_0092012 was significantly upregulated in NSCLC tissues and cell lines.
- Circ_0092012 deficiency suppressed NSCLC cell proliferation, invasion, and migration.
- Knockdown of circ_0092012 inhibited CD8+ T cell apoptosis and enhanced IFN-γ and TNF-α levels.
- Circ_0092012 acted as a sponge for miR-635, which directly targets PDL1.
- Rescue experiments confirmed that circ_0092012 knockdown's effects were mediated via the miR-635/PDL1 pathway.
- Circ_0092012 deletion suppressed tumor growth in vivo.
Conclusions:
- Circ_0092012 promotes NSCLC progression by enhancing malignant phenotypes and immune escape.
- The circ_0092012/miR-635/PDL1 axis represents a potential therapeutic target for NSCLC treatment.
