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Exosomal hsa_circ_0017252 attenuates the development of gastric cancer via inhibiting macrophage M2 polarization

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Abstract

Gastric cancer (GC) is an aggressive malignant tumor of the digestive system, with high morbidity rates. We previously demonstrated that miR-17-5p can modify tumorigenesis in GC. In addition, other studies have shown that circRNAs can regulate GC progression by sponging various miRNAs. However, the association between circRNAs and miR-17-5p in GC has not yet been explored. Hence, this study aimed to explore the possible interactions between various circRNAs and miR-17-5p using a dual-luciferase assay. CCK-8 was used to determine cell viability, and a Transwell assay was used to measure cell invasion and migration. Gene expression was assessed using quantitative reverse transcription PCR (RT-qPCR), and exosomes were identified using transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). Annexin V/PI staining was also used to detect cell apoptosis. These investigations collectively revealed that miR-17-5p is a target of the circRNA hsa_circ_0017252 and hsa_circ_0017252 is significantly downregulated in GC tissues. In addition, the overexpression of hsa_circ_0017252 inhibited GC cell migration by sponging of miR-17-5p, and GC cell-secreted exosomal hsa_circ_0017252 effectively inhibited macrophage M2-like polarization, which in turn suppressed GC cell invasion. Notably, exosomes containing hsa_circ_0017252 also suppressed GC tumor growth in vivo. Thus, our data suggest that the overexpression of hsa_circ_0017252 suppresses GC malignancy by sponging miR-17-5p. In addition, exosomal hsa_circ_0017252 excreted from GC cells attenuated GC progression by suppressing macrophage M2-like polarization. These findings improve our basic understanding of GC and open a novel avenue for developing more effective GC treatments.

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Availability of data and materials

The datasets evaluated here are all available from the corresponding author upon reasonable request.

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Funding

This study was funded by the Beijing Municipal Education Commission Science and Technology Foundation (KM202110025006).

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Authors and Affiliations

  1. Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, No. 23 Back Street, Art Museum, Beijing, 100010, China

    Jin Song, Xiaolong Xu, Shasha He, Ning Wang, Yunjing Bai, Bo Li & Shengsheng Zhang

  2. Beijing Institute of Chinese Medicine, Beijing, 100010, China

    Jin Song, Xiaolong Xu, Shasha He, Ning Wang, Yunjing Bai & Bo Li

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  1. Jin Song
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  2. Xiaolong Xu
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  3. Shasha He
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  4. Ning Wang
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  6. Bo Li
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  7. Shengsheng Zhang
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Correspondence to Bo Li or Shengsheng Zhang.

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These authors declared no competing interests.

Ethics approval and consent to participate

This study was approved by the Capital Medical University Ethics Committee (No. CMU20210402), and all GC patient and healthy control data were only collected following our receipt of their written informed consent. In addition, the Capital Medical University Ethics Committees also approved the protocol for our in vivo study (No. CMU20210405).

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Supplementary Information

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13577_2022_739_MOESM1_ESM.jpg

Supplementary file1 Supplementary Figure 1 Exosomes were isolated from GC cells. (A) The background information of hsa_circ_0017252 was listed. (B, C) NTA was applied for exosome identification. (JPG 667 KB)

13577_2022_739_MOESM2_ESM.jpg

Supplementary file2 Supplementary Figure 2 MKN45-exo-incubated macrophages decreased DUSP2 expression in tumor tissue. (A) The tumor tissues were subjected to HE staining. (B) The expression of DUSP2 was examined with IHC staining. **P<0.01 compared to MKN45, ##P<0.01 compared to MKN45 + Mexo. N = 3. (JPG 1102 KB)

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Song, J., Xu, X., He, S. et al. Exosomal hsa_circ_0017252 attenuates the development of gastric cancer via inhibiting macrophage M2 polarization. Human Cell 35, 1499–1511 (2022). https://doi.org/10.1007/s13577-022-00739-9

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  • DOI: https://doi.org/10.1007/s13577-022-00739-9

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