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Circ_0007422 Knockdown Inhibits Tumor Property and Immune Escape of Colorectal Cancer by Decreasing PDL1 Expression in a miR-1256-Dependent Manner

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Abstract

Circular RNAs (circRNAs) are a group of important molecules involved in the progression of various cancers, including colorectal cancer (CRC). Here, we aim to investigate the role and molecular mechanism of circ_0007422 in regulating CRC malignant progression. The expression levels of circ_0007422, miR-1256, and PDL1 were detected by qRT-PCR. Cell viability, proliferation, apoptosis, invasion, and self-replication ability were analyzed by CCK-8, EdU, flow cytometry, transwell, and spheroid formation experiments, respectively. Protein levels were determined by western blotting assay. CRC cells were co-cultured with CD8 + T cells, phytohemagglutinin-stimulated peripheral blood mononuclear cells (PBMCs), or cytokine-induced killer (CIK) cells in vitro, and CD8 + T-cell apoptosis, IFN-γ and TNF-α levels, and survival rate of CRC cells were analyzed to reveal the role of circ_0007422 in antitumor immunity. The relationship between miR-1256 and circ_0007422 or PDL1 was identified by a dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. A xenograft tumor model was established to verify the function of circ_0007422 in tumor growth in vivo. Immunohistochemistry (IHC) assay was used to detect positive expression rates of Ki67, E-cadherin, N-cadherin, and PDL1 expression in primary tumors from CRC cells. Circ_0007422 was upregulated in CRC tissues and cells and its knockdown inhibited proliferation, invasion, self-replication ability, and immune escape and promoted apoptosis of CRC cells. Additionally, circ_0007422 bound to miR-1256, which was identified to target PDL1. MiR-1256 inhibition reversed the effects of circ_0007422 knockdown on the tumor properties and immune escape of CRC cells. Moreover, miR-1256 introduction interacted with PDL1 to suppress proliferation, invasion, self-replication ability, and immune escape and promote apoptosis of CRC cells. Further, circ_0007422 knockdown hampered tumorigenesis of CRC cells in vivo. Circ_0007422 knockdown inhibited tumor property and immune escape of colorectal cancer through the miR-1256/PDL1 pathway, providing a potential novel therapeutic target for CRC.

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Funding

This work was supported by Nantong Municipal Commission of Health and Family Planning (QA2021010).

Nantong Municipal Commission of Health and Family Planning,QA2021010,Dian Yin

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  1. Authors Dian Yin and Li Yang contributed equally to this paper.

Authors and Affiliations

  1. Department of Oncology, Nantong First People’s Hospital, the Second Affiliated Hospital of Nantong University, Nantong City, 226000, Jiangsu, China

    Dian Yin, Li Yang, Xiu Feng, Xiaolu Zhai, Mei Hua, Jing Liu & Ying Chen

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Correspondence to Ying Chen.

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Yin, D., Yang, L., Feng, X. et al. Circ_0007422 Knockdown Inhibits Tumor Property and Immune Escape of Colorectal Cancer by Decreasing PDL1 Expression in a miR-1256-Dependent Manner. Mol Biotechnol (2024). https://doi.org/10.1007/s12033-023-01040-2

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