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Hsa_circ_0071589 aggravates stemness and oxaliplatin resistance in colorectal cancer through sponging miR-133b to upregulate SOX13 expression

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Abstract

Hsa_circ_0071589 can exacerbate the malignant behavior of colorectal cancer (CRC) cells. However, its function in stemness and oxaliplatin (OXP) resistance of CRC cells remains unclear. To assess the function of hsa_circ_0071589 in stemness and OXP resistance of CRC cells. Western blotting and qRT-PCR were applied to assess protein and mRNA levels. The association between hsa_circ_0071589, miR-133b and SOX13 was explored via a correlation analysis. Sphere formation was used to assess cell stemness. Meanwhile, the viability of CRC cells and OXP-resistant CRC cells was evaluated with the MTT assay. Cell stemness marker (CD133) levels and apoptosis of CRC cells and OXP-resistant CRC cells were tested using flow cytometry. The ALDH level was investigated using the related detection kit. In addition, the association between hsa_circ_0071589 and miR-133b and SOX13 was investigated using the RIP and dual luciferase assay. Finally, in vivo experiments were performed to detect the function of hsa_circ_0071589 in CRC, and the levels of SOX13, Ki67, and CD44 in mice were evaluated via immunohistochemistry staining. The expression of hsa_circ_0071589 and SOX13 was upregulated in CRC, whereas the expression of miR-133b was downregulated. Hsa_circ_0071589 knockdown significantly inhibited CRC stemness via the mediation of miR-133b. Moreover, hsa_circ_0071589 silencing significantly sensitized CRC cells to OXP by upregulating miR-133b. SOX13 was the direct target of miR-133b, and miR-133b could attenuate stemness and OXP resistance in CRC cells by targeting SOX13. Notably, hsa_circ_0071589 knockdown inhibited tumor growth and decreased OXP resistance in mice with CRC. Hsa_circ_0071589 aggravates stemness and OXP resistance by sponging miR-133b to indirectly target SOX13 in CRC. Thus, our study might present a novel treatment strategy against OXP-resistant CRC.

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Data availability

All data generated or analyzed during this study are included in this article. The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This work was supported by Guangxi Research Foundation for Science &Technology Base and Talent Special (No. AD20238005).

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Authors and Affiliations

  1. Department of Breast and Thyroid Surgery, Liuzhou People’s Hospital, NO.8, Wenchang Road, Liuzhou, 545006, Guangxi, People’s Republic of China

    Lv Lv

  2. Department of Dermatology & Venerology, Affiliated Hospital of Guilin Medical University, Guilin, 541001, Guangxi, People’s Republic of China

    Lu Yi

  3. Department of Gastrointestinal Surgery, Affiliated Hospital of Guilin Medical University, Guilin, 541001, Guangxi, People’s Republic of China

    Bojie Huang

  4. Clinical Medical College of Guilin Medical University, Guilin, 541001, Guangxi, People’s Republic of China

    Cong Zhou

  5. Department of Emergency and Trauma Surgery, Affiliated Hospital of Guilin Medical University, NO.15 Lequn Road, Guilin, 541001, Guangxi, People’s Republic of China

    Lei Zhang

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  4. Cong Zhou
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Contributions

LL: Conceptualization; Methodology; Validation; Formal analysis; Visualization; Supervision; LY: Investigation; Writing—Original Draft; Bojie Huang: Resources; CZ: Data Curation; LZ: Writing—Review & Editing; Project administration; Funding acquisition.

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Correspondence to Lei Zhang.

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These authors declared no competing interests in this work.

Ethical approval and consent to participate

Forty pairs of CRC and adjacent normal tissues originated from Affiliated Hospital of Guilin Medical University between August 2019 and April 2021. The Ethics Committee of Affiliated Hospital of Guilin Medical University approved this work. The data were obtained with the written informed consent. All experiments were done in accordance with NIH guide. Ethics Committees of Affiliated Hospital of Guilin Medical University approved this study.

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Lv, L., Yi, L., Huang, B. et al. Hsa_circ_0071589 aggravates stemness and oxaliplatin resistance in colorectal cancer through sponging miR-133b to upregulate SOX13 expression. Mol Cell Biochem (2023). https://doi.org/10.1007/s11010-023-04819-8

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