miR-218 overexpression suppresses tumorigenesis of papillary thyroid cancer via inactivation of PTEN /PI3K/AKT pathway by targeting Runx2

• Main Authors: Han M, Chen L, Wang Y
• Format: Article
• Language: English
• Published: Dove Medical Press 2018-09-01
• Series: OncoTargets and Therapy
• Subjects: miR-218; tumorigenesis; papillary thyroid cancer; PTEN/PI3K/AKT; Runx2
• Online Access: https://www.dovepress.com/mir-218-overexpression-suppresses-tumorigenesis-of-papillary-thyroid-c-peer-reviewed-article-OTT

Mingkun Han,* Liwei Chen,* Yang Wang Department of Otolaryngology Head and Neck Surgery, Chinese People’s Liberation Army General Hospital, Beijing 100853, China *These author contributed equally to this work Background: It was previously reported that downregulation of miR-218 promoted thyroid cancer cell invasion, migration, and proliferation. However, the biological functions of miR-218 and its possible regulatory mechanisms in papillary thyroid cancer (PTC) cells are still elusive. Materials and methods: The expression levels of miR-218 and Runx2 in PTC tissues and cells were determined by quantitative real-time PCR (qRT-PCR) and Western blot. The effects of miR-218 overexpression on cell viability, invasion, apoptosis, and PTEN/PI3K/AKT pathway in PTC cells were evaluated by cell counting kit-8 assay, Transwell invasion assay, flow cytometry assay, and Western blot, respectively. Luciferase reporter assay and qRT-PCR were performed to identify the target of miR-218. Xenograft tumor experiment was performed to confirm the biological roles of miR-218 and its potential mechanisms in vivo. Results: miR-218 expression was downregulated and Runx2 expression was upregulated in PTC tissues and cells. Overexpression of miR-218 suppressed viability and invasion, and induced apoptosis of PTC cells in vitro, while Runx2 overexpression greatly abolished these effects. miR-218 overexpression inactivated the PTEN/PI3K/AKT pathway, which was abated by Runx2 upregulation. Additionally, Runx2 was validated to be a direct target of miR-218. Moreover, enforced expression of miR-218 inhibited tumor growth and Runx2 expression, and blocked PTEN/PI3K/AKT pathway in vivo. Conclusion: miR-218 overexpression suppresses the tumorigenesis of PTC via downregulating PTEN/PI3K/AKT pathway by targeting Runx2, which indicates that miR-218 may be a potential therapeutic target for human PTC. Keywords: miR-218, papillary thyroid cancer, PTEN/PI3K/AKT, Runx2