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Updated: Mar 22, 2026

In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
PATZ1 is a target of miR-29b that is induced by Ha-Ras oncogene in rat thyroid cells
Michela Vitiello1, Teresa Valentino1, Marta De Menna2
1Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council (CNR), 80131 Naples, Italy.
Abstract:
The regulatory transcriptional factor PATZ1 is constantly downregulated in human thyroid cancer where it acts as a tumour suppressor by targeting p53-dependent genes involved in Epithelial-Mesenchymal Transition and cell migration. The aim of the present work was to elucidate the upstream signalling mechanisms regulating PATZ1 expression in thyroid cancer cells. The bioinformatics search for microRNAs able to potentially target PATZ1 led to the identification of several miRNAs. Among them we focused on the miR-29b since it was found upregulated in rat thyroid differentiated cells transformed by the Ha-Ras oncogene towards a high proliferating and high migratory phenotype resembling that of anaplastic carcinomas. Functional assays confirmed PATZ1 as a target of miR-29b, and, consistently, an inverse correlation between miR-29b and PATZ1 protein levels was found upon induction of Ha-Ras oncogene expression in these cells. Interestingly, restoration of PATZ1 expression in rat thyroid cells stably expressing the Ha-Ras oncogene decreased cell proliferation and migration, indicating a key role of PATZ1 in Ras-driven thyroid transformation. Together, these results suggest a novel mechanism regulating PATZ1 expression based on the upregulation of miR-29b expression induced by Ras oncogene.
Insights
The tumor suppressor PATZ1 is downregulated in thyroid cancer. Ras oncogene upregulates miR-29b, which targets PATZ1, promoting cancer cell proliferation and migration.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- The transcriptional factor PATZ1 functions as a tumor suppressor in human thyroid cancer.
- PATZ1 targets p53-dependent genes involved in Epithelial-Mesenchymal Transition (EMT) and cell migration.
- Understanding the regulation of PATZ1 expression is crucial for thyroid cancer research.
Purpose of the Study:
- To investigate the upstream signaling mechanisms that regulate PATZ1 expression in thyroid cancer cells.
- To identify microRNAs (miRNAs) targeting PATZ1.
- To elucidate the role of miR-29b in Ras-driven thyroid cancer.
Main Methods:
- Bioinformatic analysis to identify potential miRNA targets of PATZ1.
- Functional assays to confirm PATZ1 as a target of miR-29b.
- In vitro studies using rat thyroid cells expressing the Ha-Ras oncogene.
Main Results:
- miR-29b was identified as a key regulator targeting PATZ1.
- An inverse correlation between miR-29b and PATZ1 protein levels was observed upon Ha-Ras oncogene induction.
- Restoration of PATZ1 expression reduced proliferation and migration in Ras-transformed thyroid cells.
Conclusions:
- Ras oncogene upregulates miR-29b expression, leading to PATZ1 downregulation.
- This miR-29b-mediated downregulation of PATZ1 plays a significant role in Ras-driven thyroid transformation.
- PATZ1 acts as a crucial tumor suppressor in the context of Ras-induced thyroid cancer.
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