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Circ_0011373 promotes papillary thyroid carcinoma progression by regulating miR-1271/LRP6 axis

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Abstract

Purpose

This research aimed to explore the regulatory molecular mechanism among circular RNA (circ)_0011373, microRNA (miR)-1271, and lipoprotein receptor-related protein 6 (LRP6) in papillary thyroid carcinoma (PTC).

Methods

Quantitative real-time PCR (qRT-PCR) assay was adopted to measure the expression of circ_0011373, miR-1271, and LRP6 mRNA. Furthermore, cell cycle distribution, apoptosis, migration and invasion were investigated by flow cytometry and transwell assay, respectively. The target relationship between miR-1271 and circ_0011373 or LRP6 was predicted by using the Starbase website and DIANA TOOL and verified by dual-luciferase reporter and RIP assay. Protein expression levels of LRP6, p-mTOR, mTOR, p-AKT, AKT, p-PI3K, and PI3K were tested by Western blot. The function of circ_0011373 on PTC tumor growth was validated by the xenograft tumor model in vivo.

Results

Circ_0011373 and LRP6 were upregulated, while miR-1271 was downregulated in PTC tissues and cell lines. Moreover, knockdown of circ_0011373 inhibited cell cycle, migration, and invasion and promoted apoptosis. Of particular importance was the fact that circ_0011373 directly interacted with miR-1271 and miR-1271 inhibitor was able to reverse the effect of circ_0011373 knockdown on PTC cell progression. Meanwhile, LRP6 was directly targeted by miR-1271, and its expression was positively regulated by circ_0011373. We further confirmed that miR-1271 overexpression suppressed cell cycle, migration, and invasion and enhanced apoptosis by regulating LRP6. In addition, circ_0011373 knockdown restrained PTC tumor growth in vivo.

Conclusion

Circ_0011373 might be able to regulate PTC cell cycle, migration, invasion, and apoptosis by regulating the miR-1271/LRP6 axis.

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Data availability

The analyzed data sets generated during the present study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. The First Department of General Surgery, Affiliated Dongguan People’s Hospital, Southern Medical University(Dongguan People’s Hospital), Dongguan, Guangdong, China

    Guoxiang Huang & Xiarong Hu

  2. Department of Anesthesiolopy, Affiliated Dongguan People’s Hospital, Southern Medical University(Dongguan People’s Hospital), Dongguan, Guangdong, China

    Lijun Mao

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  1. Guoxiang Huang
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Contributions

Conceptualization and Methodology: Lijun Mao and Xiarong Hu; Formal analysis and Data curation: Lijun Mao and Xiarong Hu; Validation and Investigation: Guoxiang Huang and Lijun Mao; Writing - original draft preparation and Writing - review and editing: Guoxiang Huang, Lijun Mao and Xiarong Hu. Approval of final manuscript all authors.

Corresponding author

Correspondence to Xiarong Hu.

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Ethical approval

The present study was approved by the ethical review committee of Affiliated Dongguan People's Hospital.

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Written informed consent was obtained from all enrolled patients.

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The authors declare that they have no competing interests.

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Supplementary information

ESM 1

Figure S1 Effects of circ_0011373 knockdown on the signaling pathways in PTC cells. (A-B) Protein levels of p-mTOR, mTOR, p-AKT, AKT, p-PI3K, and PI3K in PTC cells transfected with si-NC or si-circ_0011373 were detected by western blot (a barplot, Two-way analysis of variance). ***P<0.0001. (PNG 221 kb)

High resolution image (TIF 605 kb)

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Huang, G., Mao, L. & Hu, X. Circ_0011373 promotes papillary thyroid carcinoma progression by regulating miR-1271/LRP6 axis. Hormones 22, 375–387 (2023). https://doi.org/10.1007/s42000-023-00461-7

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  • DOI: https://doi.org/10.1007/s42000-023-00461-7

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