miR-449 overexpression inhibits papillary thyroid carcinoma cell growth by targeting RET kinase-β-catenin signaling pathway

Abstract

Papillary thyroid carcinoma (PTC) is the most common thyroid cancer and represent approximately 80% of all thyroid cancers. The present study is aimed to investigate the role of microRNA (miR)-449 in the progression of PTC. Our results revealed that miR-449 was underexpressed in the collected PTC specimens compared with non-cancerous PTC tissues. Overexpression of miR-449 induced a cell cycle arrest at G0/G1 phase and inhibited PTC cell growth in vitro. Further studies revealed that RET proto-oncogene (RET) is a novel miR-449 target, due to miR-449 bound directly to its 3'-untranslated region and miR-449 mimic reduced the protein expression of RET. Similar to the effects of miR-449 overexpression, RET downregulation inhibited cell growth, whereas RET overexpression reversed the inhibitive effect of miR-449 mimic. Furthermore, miR-449 overexpression inhibited the nuclear translocation of β-catenin and reduced the expression of several downstream genes, including c-Myc, cyclin D1, T cell-specific transcription factor (TCF) and lymphoid enhancer-binding factor 1 (LEF-1), and inactivated the β-catenin pathway in TPC-1 cells. Moreover, overexpression of β-catenin prevented miR-449-reduced cell cycle arrest and cell viability. In xenograft animal experiments, miR-449 overexpression effectively suppressed the tumor growth of PTC. Taken together, our research indicated that miR-449 functions as an anti-oncogene by targeting RET, and that miR-449 overexpression inhibited the growth of PTC by inactivating the β-catenin pathway. Thus, miR-449 may serve as a potential therapeutic strategy for the treatment of PTC.

FOXE1 supports the tumor promotion of Gli2 on papillary thyroid carcinoma by the Wnt/β‐catenin pathway

“…Gli2 is the key mediator of Hh-signaling pathway, which is highly conserved in embryonic development, whereas its activation is involved in glioma, BCCs, medulloblastomas, and rhabdomyosarcoma (Boehme et al, 2016;Danhof, Lewis, & Brown, 2017;Raducu et al, 2016;Xu et al, 2017 as our previous study showed (Z. Li et al, 2016). In line with our suspicions, here we found that Gli2 gene knockdown reduces the levels of molecules implicated in the Wnt/β-catenin pathway.…”

“…EpiQuik Nuclear Extraction Kit(EpiGentek, Brooklyn, NY).Western blot analysis was performed as previously described(Z. Li et al, 2016). The FOXE1, Gli2, PCNA, Ki-67, Wnt5a, and β-catenin proteins were detected by using anti-FOXE1 (ab134129; Abcam), anti-Gli2 (ab167389; Abcam), anti-PCNA (ab18197; Abcam), anti-Ki-67 (ab15580; Abcam), anti-Wnt5a (ad72583; Abcam), and anti-β-catenin (ab16051; Abcam) polyclonal antibodies, respectively.…”

Activation of the ROCK1/MMP-9 pathway is associated with the invasion and poor prognosis in papillary thyroid carcinoma

“…Papillary thyroid carcinoma (PTC) is the most common thyroid carcinoma, accounting for approximately 80% of all thyroid malignant tumors (1)(2)(3)(4). Despite highly curable and presenting a 10-year survival rate more than 90%, lymph node metastasis, especially in the neck, occurs in 20-50% of all tumor patients and regional recurrence is found in 5-20% of patients who have undergone total thyroidectomy (3,5,6).…”

MicroRNA‑449b‑3p inhibits epithelial‑mesenchymal transition by targeting IL‑6 and through the JAK2/STAT3 signaling pathway in non‑small cell lung cancer

“…For example, miR-449 shows atypical levels in many cancer types with variations between different tumors. miR-449 plays an important role in gynecological clear cell carcinoma (14), hepatocellular cancer (15), papillary thyroid carcinoma (16) and breast cancer (17). Despite this evidence, the mechanism of action in NSCLC remains to be established.…”