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miR-29a inhibits proliferation, invasion, and migration of papillary thyroid cancer by targeting DPP4
Yufei Wang1, Jie Han1, Yuetao Lv1
1Department of Breast and Thyroid Surgery, Jining NO.1 People's Hospital, Affiliated Jining NO.1 People's Hospital of Jining Medical University, Jining Medical University, Jining City, Shandong Province 272011, People's Republic of China.
Abstract:
Purpose: The purpose of this study was to investigate the effects of miR-29a on papillary thyroid cancer (PTC) and its underlying mechanisms. Methods: Primary tumor tissues and adjacent tissues of 69 patients with PTC were obtained. Human thyroid cell line Nthy-ori3-1 and PTC cell lines K1, BCPAP, TPC-1 were cultured. K1 cells were transfected and divided into following groups: blank group (without any treatment), miR-29a mimics group, control mimics group, miR-29a inhibitor group, control inhibitor group, DPP4 siRNA group, control siRNA group and miR-29a inhibitor + DPP4 siRNA group. qRT-PCR and Western blot were used to detect miR-29a and DPP4 expression. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and transwell assay were performed to detect cells proliferation, migration, and invasion. A nude mice xenograft experiment was performed. Results: miR-29a was significantly downregulated in PTC tissues, K1 and TPC-1 cells (P<0.01). DPP4 was significantly upregulated in the miR-29a inhibitor group and significantly downregulated in the miR-29a mimics group (P<0.01). DPP4 was the target gene of miR-29a. miR-29a significantly inhibited K1 cell proliferation, invasion, migration and PTC growth in nude mice by targeting DPP4 (P<0.01). Conclusion: miR-29a inhibits proliferation, migration, and invasion of PTC by targeting DPP4, which might provide a new target for clinical treatment of PTC.
Insights
MicroRNA-29a (miR-29a) is downregulated in papillary thyroid cancer (PTC). Restoring miR-29a inhibits PTC cell proliferation and growth by targeting DPP4, offering a potential new therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Papillary thyroid cancer (PTC) is the most common type of thyroid malignancy.
- Understanding the molecular mechanisms underlying PTC progression is crucial for developing effective treatments.
- MicroRNAs (miRNAs) play significant roles in cancer development and progression.
Purpose of the Study:
- To investigate the role of miR-29a in papillary thyroid cancer (PTC).
- To elucidate the underlying molecular mechanisms of miR-29a's action in PTC.
- To identify potential therapeutic targets for PTC treatment.
Main Methods:
- Analysis of miR-29a and DPP4 expression in PTC tissues and cell lines using qRT-PCR and Western blot.
- In vitro assays (MTT, Transwell) to assess cell proliferation, migration, and invasion.
- In vivo xenograft experiments in nude mice to evaluate tumor growth.
- Transfection of PTC cell lines with miR-29a mimics, inhibitors, and DPP4 siRNA.
Main Results:
- miR-29a was significantly downregulated in PTC tissues and cell lines.
- DPP4 expression was inversely correlated with miR-29a levels, indicating DPP4 as a direct target gene.
- Overexpression of miR-29a suppressed PTC cell proliferation, migration, and invasion.
- miR-29a significantly inhibited tumor growth in a preclinical mouse model.
Conclusions:
- miR-29a acts as a tumor suppressor in PTC by inhibiting cell proliferation, migration, and invasion.
- The inhibitory effects of miR-29a are mediated through the targeting of DPP4.
- miR-29a represents a promising novel therapeutic target for papillary thyroid cancer.
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