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CircGLIS3 inhibits thyroid cancer invasion and metastasis through miR-146b-3p/AIF1L axis

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Abstract

Purpose

Studies have shown that circRNA is involved in the occurrence and development of human cancers. However, it remains unclear that the contribution of circRNA in thyroid carcinoma and its role in the process of tumorigenesis.

Methods

The expression profile of circRNA-miRNA-mRNA in thyroid carcinoma was detected by RNA sequencing and verified by qRT-PCR. The characteristics of circGLIS3 were verified by RNase R and actinomycin assays, subcellular fractionation, and fluorescence in situ hybridization. The functions of circGLIS3 and AIF1L were detected by wound healing, transwell, 3D culture and Western blot. RNA Immunoprecipitation (RIP), RNA pulldown and dual-luciferase reporter assays were used to verify the target genes of circGLIS3 and downstream miRNAs. Functional rescue experiments were performed by transfecting miRNA mimics or siRNA of target genes. Finally, metastatic mouse models were used to investigate circGLIS3 function in vivo.

Results

In this study, we discovered a novel circRNA (has_circ_0007368, named as circGLIS3) by RNA sequencing. CircGLIS3 was down-regulated in thyroid carcinoma tissues and cells line, and was negatively associated with malignant clinical features of thyroid carcinoma. Functional studies found that circGLIS3 could inhibit the migration and invasion of thyroid carcinoma cells, and was related to the EMT process. Mechanistically, circGLIS3 can upregulate the expression of the AIF1L gene by acting as a miR-146b-3p sponge to inhibit the progression of thyroid carcinoma.

Conclusion

Our study identified circGLIS3 as a novel tumor suppressor in thyroid cancer, indicating the potential of circGLIS3 as a promising diagnostic and prognostic marker for thyroid cancer.

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Data Availability

The data in the present study is available from the corresponding author upon reasonable request.

Abbreviations

DTC:

Differentiated thyroid carcinoma

circRNAs:

Circular RNAs

EMT:

Epithelial-mesenchymal transition

RBPs:

RNA binding proteins

PTC:

Papillary thyroid carcinoma

ceRNA:

Competing endogenous RNA

ATC:

Anaplastic thyroid carcinoma

FBS:

Fetal bovine serum

NC:

Negative control

FISH:

Fluorescence in situ hybridization

3D:

Three-dimensional

RIP:

RNA immunoprecipitation

SD:

Standard deviation

gDNA:

Genomic DNA

AIF1L:

Allograft inflammatory factor 1 like

IBA2:

Ionized calcium-binding adapter molecule 2

AIF1:

Allograft inflammatory factor 1

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Funding

This work was funded by the National Natural Science Foundation of China (No.81772850 and No.82273300) and Medical Science and Technology Research Fund of Guangdong Province (A2021127).

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Author notes

  1. Siting Cao and Yali Yin contributed equally to this work.

Authors and Affiliations

  1. Department of Endocrinology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China

    Siting Cao, Huijuan Hu, Shubin Hong, Weiman He, Yanbing Li, Shuang Yu & Haipeng Xiao

  2. Department of Endocrinology, Peking University Shenzhen Hospital, Shenzhen, 518036, China

    Yali Yin

  3. Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China

    Weiming Lv

  4. Institute of Precision Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China

    Rengyun Liu

Authors
  1. Siting Cao
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Contributions

S.C. and Y.Y. performed the experiments and drafted the manuscript; H.H. and W.H. provided experimental support; W.L. collected the clinical specimens; S.H., R.L. and Y.L. commented on the study; S.Y. and H.X. designed and supervised the study and revised the manuscript. All authors reviewed the manuscript.

Corresponding authors

Correspondence to Shuang Yu or Haipeng Xiao.

Ethics declarations

Ethics approval and consent to participate

The study, which involved human samples, obtained approval from the Institutional Research Ethics Committee of Sun Yat-sen University. Animal Experiment were carried out in accordance with the National Research Council’s Guide for the Care and Use of Laboratory Animals and were conducted with the approval of the Ethics Committee of Sun Yat-sen University.

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The authors declare no potential conflicts of interest.

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Cao, S., Yin, Y., Hu, H. et al. CircGLIS3 inhibits thyroid cancer invasion and metastasis through miR-146b-3p/AIF1L axis. Cell Oncol. 46, 1777–1789 (2023). https://doi.org/10.1007/s13402-023-00845-2

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