ArticleMolecular therapy. Nucleic acids2021
Testicular orphan receptor 4 (TR4) promotes papillary thyroid cancer invasion via activating circ-FNLA/miR-149-5p/MMP9 signaling.
Article in Molecular therapy. Nucleic acids, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- Clinical significance of matrix metalloproteinase-9 expression in papillary thyroid carcinoma: a meta-analysis.World journal of surgical oncology · 2023Pooled it
- Adipocyte promotes tumor cell invasion and metastasis via FATP2: a novel cell-cell interaction in papillary thyroid carcinoma.Gland surgery · 2026Article
- CircUCK2(2,3) promotes cancer progression and enhances synergistic cytotoxicity of lenvatinib with EGFR inhibitors via activating CNIH4-TGFα-EGFR signaling.Cellular & molecular biology letters · 2025Article
- Multi-disease transcriptomic analysis of sex hormone genes reveals a novel prognostic model for thyroid cancer with breast cancer correlations.Frontiers in oncology · 2025Article
- Matrix Metalloproteinase 9/microRNA-145 Ratio: Bridging Genomic and Immunological Variabilities in Thyroid Cancer.Biomedicines · 2023Article
- N-linked glycosylation is essential for anti-tumor activities of KIAA1324 in gastric cancer.Cell death & disease · 2023Article
- The Role of MMP-9 and MMP-9 Inhibition in Different Types of Thyroid Carcinoma.Molecules (Basel, Switzerland) · 2023Review
- Hsa_circ_0003602 Contributes to the Progression of Colorectal Cancer by Mediating the miR-149-5p/SLC38A1 Axis.Gut and liver · 2023Article
- Androgen receptor suppresses lung cancer invasion and increases cisplatin responseInternational journal of biological sciences · 2023Article
- Vitamin D inhibits osteosarcoma by reprogramming nonsense-mediated RNA decay and SNAI2-mediated epithelial-to-mesenchymal transition.Frontiers in oncology · 2023Article
- Tumor-Suppressive and Oncogenic Roles of microRNA-149-5p in Human Cancers.International journal of molecular sciences · 2022Review
- Enhancement of LncRNA-HFRL expression induces cardiomyocyte inflammation, proliferation, and fibrosis via the sequestering of miR-149-5p-mediated collagen 22A inhibition.Annals of translational medicine · 2022Article
- Estrogen receptor beta promotes lung cancer invasion via increasing CXCR4 expression.Cell death & disease · 2022Article
- Curcumin Inhibits Papillary Thyroid Cancer Cell Proliferation by Regulating lncRNA LINC00691.Analytical cellular pathology (Amsterdam) · 2022Article
- A Review on the Role of miR-149-5p in the Carcinogenesis.International journal of molecular sciences · 2021Review
- MiR-149-5p: An Important miRNA Regulated by Competing Endogenous RNAs in Diverse Human Cancers.Frontiers in oncology · 2021Review
- miR-616-5p Promotes Invasion and Migration of Bladder CancerFrontiers in oncology · 2021Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The incidence and mortality of papillary thyroid cancer (PTC) have steadily increased. Although conventional therapies are very effective toward differentiated PTC patients, very limited therapeutic options are applicable to those patients with distant metastases. Therefore, better understanding of the molecular biology of metastatic PTC helps identify novel targets and facilitates the development of new therapies. In this study, we first found that testicular orphan receptor 4 (TR4) was significantly increased in PTC tumors spreading to lymph nodes compared to the paired primary tumors. Experimental evidence suggested that TR4 drove PTC progression via promoting its cell invasion and cell migration. Mechanistically, TR4 transcriptionally regulated the expression level of circ-filamin A (FLNA), which competed with matrix metalloproteinase 9 (MMP9) for microRNA (miR)-149-5p binding and led to an increased protein level of MMP9. Interruption assays with various gene manipulations verified that the TR4/circ-FLNA/miR-149-5p/MMP9 signaling axis played a central role in cell invasion and cell migration of PTC cells. Moreover, a xenografted mouse model also confirmed that the TR4/circ-FLNA signal promoted PTC tumor growth. Overall, our study pinpoints the oncogenic role of TR4 in PTC development, and the targeting of TR4/circ-FLNA/miR-149-5p/MMP9 signaling may be an alternative option for metastatic PTC patients.
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