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Exosomal Circ_FMN2 Derived from the Serum of Colorectal Cancer Patients Promotes Cancer Progression by miR-338-3p/MSI1 Axis

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A Correction to this article was published on 27 September 2023

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Abstract

Background: Colorectal cancer (CRC) is a common malignancy of the gastrointestinal tract with high incidence and mortality. Exosomal circular RNA (circRNA) has been shown to be associated with the malignant progression of cancers, including CRC. Circ_0005100 (named as circ_FMN2) has been shown to promote CRC cell proliferation and migration. However, whether exosomal circ_FMN2 participated in CRC progression remains unclear. Methods: Exosomes were isolated from the serum of CRC patients and then identified using transmission electron microscope. Western blot assay was used to test the protein levels of exosome markers, proliferation-related marker, metastasis-related markers and musashi-1 (MSI1). The expression levels of circ_FMN2, microRNA (miR)-338-3p and MSI1 were detected by qPCR. Flow cytometry, colony formation assay, MTT assay, and transwell assay were employed to measure cell cycle, apoptosis, colony formation ability, viability, migration and invasion. Dual-luciferase reporter assay was performed to assess the interaction between miR-338-3p and circ_FMN2 or MSI1. BALB/c nude mice was used to conduct animal experiments. Results: Circ_FMN2 was overexpressed in the exosomes of CRC patient’s serums and CRC cells. Overexpressed exosomal circ_FMN2 could promote CRC cell proliferation, metastasis, and suppress apoptosis. Circ_FMN2 acted as miR-338-3p sponge. MiR-338-3p overexpression reversed the promotion effect of circ_FMN2 on CRC progression. MSI1 was found to be a target of miR-338-3p, and its overexpression revoked the inhibitory effect of miR-338-3p on CRC progression. Furthermore, exosomal circ_FMN2 overexpression also could facilitate CRC tumor growth in vivo. Conclusion: Exosomal circ_FMN2 accelerated CRC progression through miR-338-3p/MSI1 axis, revealing that exosomal circ_FMN2 might be a target for CRC treatment.

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Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

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Funding

This research was supported by the Natural Science Foundation of Hebei Province (H2020206311) and the Central Guiding Local Science and Technology Development Fund Project (Hebei Science and Technology Department Project) (226Z7712G).

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Authors and Affiliations

  1. Department of Research, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China

    Qiyao Yu

  2. Department of Physiology, Hebei Medical University, Shijiazhuang, 050011, Hebei Province, China

    Yi Zhang & Yanming Tian

  3. Department of Radiation Oncology, The Fourth Hospital of Hebei Medical University, No. 12, Jian Kang Road, Shijiazhuang, 050011, Hebei Province, China

    Ale Peng, Xiujing Cui, Boyue Ding, Lei Yang & Chao Gao

  4. Department of Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China

    Yabin Liu

  5. Department of experimental animal center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China

    Yingchao Ju

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Correspondence to Chao Gao.

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The design of this protocol follows the tenets of the Declaration of Helsinki, approved by the Ethics Committee of The Fourth Hospital of Hebei Medical University.

Animal experiments were approved by the Animal Ethics Committee of The Fourth Hospital of Hebei Medical University.

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Supplementary Fig. 1

The Detection of the Stability and size of Exosomes. (A-B) NTA Analysis was used to Assess the size of Exo-HV and Exo-CRC. (C) The expression of exosomal circ_FMN2 was examined by qRT-PCR after placing blood samples at room temperature 0 h, 6 h, 12 h, and 24 h. (D) The expression of exosomal circ_FMN2 was determined by qRT-PCR after freezing and thawing blood samples repeatedly 0 cycle, 2 cycles, 4 cycles and 8 cycles.

Supplementary Fig. 2

The representative pictures for Fig. 2I (A), 2 J-K (B-C), 4I-J (D-E) and 6I-J (F-G).

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Yu, Q., Zhang, Y., Tian, Y. et al. Exosomal Circ_FMN2 Derived from the Serum of Colorectal Cancer Patients Promotes Cancer Progression by miR-338-3p/MSI1 Axis. Appl Biochem Biotechnol 195, 7322–7337 (2023). https://doi.org/10.1007/s12010-023-04456-3

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