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CircRTN1 acts as a miR-431-5p sponge to promote thyroid cancer progression by upregulating TGFA

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Abstract

Purpose

This study aimed to explore the role and underlying mechanism of circular RNA (circRNA) reticulon 1 (circRTN1) in thyroid cancer (TC).

Methods

The expression levels of circRTN1, microRNA-431-5p (miR-431-5p), and transforming growth factor-alpha (TGFA) mRNA were measured by quantitative real-time PCR (qRT-PCR). Cell proliferation was evaluated using colony formation and 5-ethynyl-2’-deoxyuridine (EdU) assays. Cell apoptosis was analyzed using flow cytometry. Cell migration and invasion were measured using the transwell assay. The protein levels of ki-67, Bax, matrix metalloproteinase 2 (MMP-2), and TGFA were detected using Western blot assay. The interaction between miR-431-5p and circRTN1 or TGFA was verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. The effect of circRTN1on TC in vivo was explored via xenograft tumor assay.

Results

The expression of circRTN1 was increased in TC tissues and cells. Knockdown of circRTN1 suppressed TC cell proliferation, migration, and invasion, and increased cell apoptosis. MiR-431-5p was a target of circRTN1, and miR-431-5p downregulation reversed the role of circRTN1 knockdown in TC cells. TGFA was identified as a direct target of miR-431-5p, and miR-431-5p exerted the anti-tumor role in TC cells by downregulating TGFA. Moreover, circRTN1 sponged miR-431-5p to regulate TGFA expression. Furthermore, circRTN1 knockdown inhibited tumor growth in vivo.

Conclusion

CircRTN1 acted as a cancer-promoting circRNA in TC by regulating the miR-431-5p/TGFA axis, providing a potential therapeutic strategy for TC treatment.

Highlights

  • CircRTN1 was highly expressed in thyroid cancer tissues and cells.

  • CircRTN1 knockdown inhibited thyroid cancer progression by sponging miR-431-5p.

  • MiR-431-5p targeted TGFA to exert the anti-cancer role in thyroid cancer cells.

  • CircRTN1 regulated TGFA expression by acting as a sponge of miR-431-5p.

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Authors and Affiliations

  1. Department of Radiation Oncology, the First Affiliated Hospital of Anhui Medical University, No.218, Jixi Road, Hefei, 230022, Anhui, China

    Yu Gao, Yichun Wang, Lei Xu, Xiaoque Xie, Liyang Zhu & Fan Wang

Authors
  1. Yu Gao
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  2. Yichun Wang
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  3. Lei Xu
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  4. Xiaoque Xie
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  5. Liyang Zhu
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  6. Fan Wang
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Corresponding author

Correspondence to Fan Wang.

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Written informed consent was obtained from all participants. This study was approved by the Ethics Committee of the First Affiliated Hospital of Anhui Medical University Hefei, Anhui, China.

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The authors declare no competing interest.

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Supplementary Figure 1. The effects of cabozantinib and TSH on the expression of circRTN1

. (A and B) The expression of circRTN1 was detected by qRT-PCR in TPC-1 cells treated with different doses of cabozantinib and TSH (ANOVA). All data are shown as mean ± SD.

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Gao, Y., Wang, Y., Xu, L. et al. CircRTN1 acts as a miR-431-5p sponge to promote thyroid cancer progression by upregulating TGFA. Hormones 21, 611–623 (2022). https://doi.org/10.1007/s42000-022-00378-7

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  • DOI: https://doi.org/10.1007/s42000-022-00378-7

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