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Microarray profiling identifies hsa_circ_0082003 as a novel tumor promoter for papillary thyroid carcinoma

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Abstract

Background

Circular RNAs (circRNAs) are non-coding RNAs that have essential regulatory roles in the development of various tumors. This study explored whether circRNAs are involved in the progression of papillary thyroid carcinoma (PTC).

Methods

Differentially expressed circRNAs (DECs) in four pairs of PTC and matched normal thyroid tissues were screened using a circRNA microarray. The potential functions of dysregulated circRNAs were predicted by bioinformatic analyses. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used to determine hsa_circ_0082003 expression in 80 pairs of PTC and matched normal thyroid tissues. Cell counting kit-8, colony formation, wound healing, and Transwell assays were performed to evaluate the biological functions of hsa_circ_0082003 in PTC cells. The role of hsa_circ_0082003 in PTC tumorigenesis in vivo was validated in nude mice.

Results

In total, 3150 DECs (2317 upregulated and 833 downregulated) were identified. Pathway enrichment analyses indicated that the dysregulated circRNAs may play roles in PTC development. RT-qPCR validation demonstrated that hsa_circ_0082003 expression was significantly increased in PTC tissues and correlated with poor clinicopathological parameters. Receiver operating characteristic curve analysis showed that hsa_circ_0082003 had good performance for diagnosing PTC and judging whether it was accompanied by lymph node metastasis. Knockdown of hsa_circ_0082003 inhibited PTC cell proliferation, migration, and invasion. Tumor formation assays in vivo showed that downregulation of hsa_circ_0082003 significantly suppressed the growth of PTC.

Conclusion

Hsa_circ_0082003 may serve as a novel diagnostic biomarker and potential therapeutic target for PTC.

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Data availability

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

Abbreviations

AUC:

Area under the receiver operating characteristic curve

BP:

Biological process

CC:

Cellular component

CI:

Confidence interval

circRNA:

Circular RNA

DEC:

Differentially expressed circRNA

ECM:

Extracellular matrix

ETE:

Extra-thyroidal extension

FBS:

Fetal bovine serum

GO:

Gene ontology

KEGG:

Kyoto encyclopedia of genes and genomes

LNM:

Lymph node metastasis

MF:

Molecular function

miRNA:

MicroRNA

NC:

Negative control

NS:

Not statistically significant

PBS:

Phosphate buffered saline

PTC:

Papillary thyroid carcinoma

pTNM:

Pathological tumor, node, and metastasis

ROC:

Receiver operating characteristic

RPMI:

Roswell park memorial institute

RT-qPCR:

Reverse transcription quantitative polymerase chain reaction

shRNA:

Short hairpin RNA

siRNA:

Small interfering RNA

TC:

Thyroid carcinoma

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Acknowledgements

We would like to thank Editage (www.editage.cn) for English language editing.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Author notes

  1. J. Ye and J.-W. Feng contributed equally to this work.

Authors and Affiliations

  1. Department of Thyroid Surgery, The Third Affiliated Hospital of Soochow University, Changzhou First People’s Hospital, Changzhou, Jiangsu, China

    J. Ye, J.-W. Feng, W.-X. Wu, G.-F. Qi, F. Wang, J. Hu, L.-Z. Hong, S.-Y. Liu & Y. Jiang

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Contributions

Conceptualization and experimental design: YJ and JY; Experimentation: JY, JWF, WXW, and GFQ; Data analysis and manuscript writing: JY and JWF; Contribution of reagents/materials/analysis tools: JH, LZH, FW, and SYL; All authors have read and approved the final manuscript.

Corresponding author

Correspondence to Y. Jiang.

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Conflict of interest

This manuscript has not been published nor submitted for publication elsewhere. All authors have contributed significantly, and agree with the content of the manuscript. The authors report no proprietary or commercial interest in any product mentioned or concept discussed in this article.

Ethical approval

This study was approved by the Ethical Committee of Changzhou First People’s Hospital and was performed according to the ethical standards laid down in the 1964 Declaration of Helsinki.

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Informed consent was obtained from all study participants.

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Supplementary Information

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40618_2022_1922_MOESM1_ESM.xls

Table S1 Detailed information on the 10 most significantly upregulated circRNAs in PTC tissues as compared with matched normal thyroid tissues (XLS 24 KB)

40618_2022_1922_MOESM2_ESM.tif

Fig. S1 hsa_circ_0082003 has no significant effect on the proliferation, migration, and invasion of the human normal thyroid cell line in vitro. A RT-qPCR analysis of the transfection efficiency in the Nthy-ori 3–1 cell line. Relative expression levels were normalized to GAPDH expression. B CCK-8 assay of Nthy-ori 3–1 cells transfected with sh-hsa_circ_0082003 or sh-NC at the indicated time points. Wound healing assay (C) and Transwell invasion assay (D) of Nthy-ori 3–1 cells transfected with sh-hsa_circ_0082003 or sh-NC, respectively. NS, not statistically significant. ***P < 0.001 (TIF 9138 KB)

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Ye, J., Feng, JW., Wu, WX. et al. Microarray profiling identifies hsa_circ_0082003 as a novel tumor promoter for papillary thyroid carcinoma. J Endocrinol Invest 46, 509–522 (2023). https://doi.org/10.1007/s40618-022-01922-3

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