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miR-329 inhibits papillary thyroid cancer progression via direct targeting WNT1
Liang Wu1, Fulai Pei1, Xiaojuan Men2
1Department of Oncology, Linyi Central Hospital, Linyi, Shandong 276400, P.R. China.
Abstract:
Dysregulated microRNA-329 (miR-329) serves an important role in the progression of certain types of tumor. However, the exact function and mechanisms of miR-329 in papillary thyroid cancer (PTC) remain unknown. The present study investigated the function and mechanisms of miR-329 in regulating PTC cell progression. The results revealed that the expression of miR-329 was significantly downregulated in PTC tissues and cell lines compared with adjacent normal tissues and a human immortalized follicular cell line. miR-329 mimics notably decreased PTC cell proliferation, colony formation and WNT1 expression in vitro, as well as suppressing PTC tumor growth in vivo. In addition, luciferase assays determined that miR-329 was able to directly bind with the 3'untranslated region of WNT1. Furthermore, short interfering RNA-WNT1-induced downregulation of WNT1, which demonstrated similar effects to miR-329 overexpression. WNT1 overexpression rescued the tumor suppressive effects of miR-329 in PTC cells. The present study provided new insights into the role of miR-329 in PTC progression and suggests the potential application of miR-329 as a therapy for PTC.
Insights
MicroRNA-329 (miR-329) is downregulated in papillary thyroid cancer (PTC). Restoring miR-329 inhibits PTC cell growth and tumor development by targeting WNT1, suggesting its therapeutic potential.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Dysregulated microRNA-329 (miR-329) is implicated in tumor progression.
- The specific role of miR-329 in papillary thyroid cancer (PTC) is not well understood.
Purpose of the Study:
- To investigate the function and regulatory mechanisms of miR-329 in PTC.
- To explore the potential of miR-329 as a therapeutic agent for PTC.
Main Methods:
- Quantitative real-time PCR to assess miR-329 expression in PTC tissues and cell lines.
- In vitro assays (proliferation, colony formation) and in vivo tumor growth studies.
- Luciferase reporter assays to confirm direct binding of miR-329 to WNT1 3'UTR.
- Experiments using short interfering RNA (siRNA) for WNT1 and WNT1 overexpression vectors.
Main Results:
- miR-329 expression was significantly downregulated in PTC tissues and cell lines.
- miR-329 mimics suppressed PTC cell proliferation, colony formation, and tumor growth in vivo.
- miR-329 directly targets the 3'untranslated region of WNT1.
- WNT1 knockdown mimicked miR-329 overexpression effects, and WNT1 overexpression reversed miR-329's tumor-suppressive actions.
Conclusions:
- miR-329 acts as a tumor suppressor in PTC by inhibiting cell proliferation and growth.
- The miR-329/WNT1 axis is a key regulatory pathway in PTC progression.
- miR-329 holds promise as a potential therapeutic target for papillary thyroid cancer.
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