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Updated: Jul 18, 2025
In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
CircGLIS3 inhibits thyroid cancer invasion and metastasis through miR-146b-3p/AIF1L axis
Siting Cao1, Yali Yin2, Huijuan Hu1
1Department of Endocrinology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China.
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.
Insights
This study identifies circGLIS3 as a novel tumor suppressor in thyroid cancer. Down-regulation of circGLIS3 correlates with malignancy, and it inhibits cancer progression by sponging miR-146b-3p to upregulate AIF1L.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Circular RNAs (circRNAs) are implicated in human cancer development.
- The specific role of circRNAs in thyroid carcinoma tumorigenesis remains largely unknown.
Purpose of the Study:
- To investigate the role and mechanism of circRNAs in thyroid carcinoma.
- To identify novel circRNAs involved in thyroid cancer progression.
Main Methods:
- RNA sequencing and qRT-PCR to profile circRNA-miRNA-mRNA expression.
- Functional assays (wound healing, transwell, 3D culture) to assess circGLIS3's role in cell migration and invasion.
- Molecular mechanism studies including RNA immunoprecipitation and luciferase reporter assays to elucidate target interactions.
- In vivo studies using metastatic mouse models.
Main Results:
- A novel circRNA, circGLIS3 (has_circ_0007368), was identified and found to be downregulated in thyroid carcinoma tissues and cell lines.
- Decreased circGLIS3 expression was associated with malignant clinical features.
- CircGLIS3 inhibited thyroid carcinoma cell migration and invasion, and was linked to the epithelial-mesenchymal transition (EMT) process.
- Mechanistically, circGLIS3 acts as a sponge for miR-146b-3p, upregulating AIF1L expression and suppressing tumor progression.
Conclusions:
- CircGLIS3 functions as a tumor suppressor in thyroid cancer.
- CircGLIS3 holds potential as a diagnostic and prognostic biomarker for thyroid cancer.
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