FOXN3 suppresses the growth and invasion of papillary thyroid cancer through the inactivation of Wnt/β-catenin pathway

Zhao, Chuanqi; Mo, Liping; Li, Chao; Han, Shui-Ping; Zhao, Wenbo; Liu, Lifeng

doi:10.1016/j.mce.2020.110925

Cited by 19 publications

(20 citation statements)

References 32 publications

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“…He and his research team reported a notable decrease in FOXN3 expression in adult acute myeloid leukemia and their data revealed that FOXN3 exerted tumor-suppressing roles by inhibiting cell proliferation and promoting apoptosis [ 11 ]. Zhao et al reported that decreased FOXN3 expression was observed in papillary thyroid cancer and discovered that FOXN3 inhibited tumor cell growth and invasion via the inactivation of Wnt/ β-catenin pathway [ 13 ]. Moreover, researches by Chen et al [ 14 ] and Sun et al [ 15 ] manifested that FOXN3 repressed tumor cell proliferation and epithelial-to-mesenchymal transition as well as metastasis in melanoma and tongue squamous cell carcinoma.…”

Section: Discussionmentioning

confidence: 99%

“…It is well documented that Forkhead box N3 (FOXN3) belongs to the FOX family of transcriptional factors, which are implicated in a great variety of biological activities, including cell survival, cell proliferation and cell migration as well as cell invasion [ 10 – 12 ]. Recent studies have uncovered that FOXN3 functions as a key player in multiple kinds of malignant tumors, such as papillary thyroid cancer [ 13 ], tongue squamous cell carcinoma [ 14 ], melanoma [ 15 ] and breast cancer [ 16 ]. Nevertheless, potential biological functions of FOXN3 in human glioma remain largely unclear.…”

Section: Introductionmentioning

confidence: 99%

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FOXN3 inhibits cell proliferation and invasion via modulating the AKT/MDM2/p53 axis in human glioma

Wang

Yang

et al. 2021

Aging

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This study aimed to evaluate the biological role of forkhead box N3 (FOXN3) in human glioma and clarify the possible molecular mechanisms. FOXN3 expression patterns in clinical tissue specimens were characterized via qPCR and Western blotting. Kaplan-Meier survival curve was applied to assess the correlation between FOXN3 expression and overall survival. Effects of FOXN3 over-expression and depletion on glioma cell proliferation, apoptosis, migration and invasion were assessed by CCK8, colony formation assay, flow cytometry, scratch wound healing assay and Transwell invasion assay, respectively. Moreover, the involvement of AKT/murine double minute 2 (MDM2)/p53 pathway was evaluated. Additionally, tumor transplantation model assay was performed to determine the effects of FOXN3 over-expression on glioma cell growth in vivo . Results showed that FOXN3 was significantly down-regulated in glioma tissues compared with normal tissues. Patients with lower FOXN3 expression exhibited a shorter overall survival time. Gain- and loss-of-function analyses demonstrated that FOXN3 over-expression significantly suppressed proliferation, survival and motility of glioma cells, whereas FOXN3 knockdown remarkably promoted glioma cell proliferation, survival and motility. Furthermore, FOXN3 over-expression inhibited the activation of AKT/MDM2/p53 signaling pathway in glioma cells, while FOXN3 depletion facilitated its activation. Additionally, tumor xenograft assays revealed that FOXN3 over-expression retarded glioma cell growth in vivo . Collectively, these findings indicate that FOXN3 inhibits cell growth and invasion through inactivating the AKT/MDM2/p53 signaling pathway and that FOXN3-AKT/MDM2/p53 axis may represent a novel therapeutic target for glioma patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

FOXN3 inhibits cell proliferation and invasion via modulating the AKT/MDM2/p53 axis in human glioma

Wang

Yang

et al. 2021

Aging

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“…It is well established -catenin signaling was implicated in a variety of human cancers. There is -catenin signaling is closely related to the progression of TC -catenin has been identified as the downstream effector of Wnt signaling, which can activate cyclin D1 to promote the growth and metastasis of TC [25]. Activation of -catenin signaling could overturn the inhibitory effect of forkhead box N3 on TC progression, -catenin signaling in TC [25].…”

Section: Discussionmentioning

confidence: 99%

Silencing of AHNAK2 restricts thyroid carcinoma progression by inhibiting the Wnt/β-catenin pathway

Lin

Hou

et al. 2021

neo

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AHNAK nucleoprotein 2 (AHNAK2) has been proposed to have an oncogenic role in various human cancers. However, the functional role of AHNAK2 in thyroid carcinoma (TC) progression has never been explored. In this study, quantitative real-time polymerase chain reaction and western blot were conducted to evaluate the expression of genes. The functional role of AHNAK2 was elucidated by cell count kit-8, colony-forming assay, wound healing assay, and Transwell invasion assay. We found that AHNAK2 was highly expressed in thyroid carcinoma, and it was tightly correlated with the pathological stage in TC. The mRNA and protein leve ls of AHNAK2 were increased in TC cells. Silencing of AHNAK2 restricted the proliferation, metastasis, and epithelial-mesenchymal transition (EMT) of TC cells. AHNAK2 silencing inhibited the protein -catenin and cyclin D1, and AHNAK2 overexp ression had the opposite effects. Moreover, LiCl or ICG-001 exposure counteracted the effects of AHNAK2 silencing or upregulation on malignant phenotypes of TC cells. In conclusion, the knockdown of AHNAK2 restrained the proliferation, metastasis, and EMT -catenin pathway, providing a new potential mechanism of AHNAK2 in understanding the oncogenesis and progression of TC. Key words: AHNAK nucleoprotein 2; thyroid carcinoma; epithelial-mesenchymal transition;-catenin pathway Thyroid cancer (TC) is one of the common malignancies occurring in the e ndocrine system, and its incidence continues to rise in the past 40 years [1]. Papillary thyroid carcinoma is the most common histological type, occupying about 90% of TC [2]. Although most TC patients can be treated by surgical operation and radioactive iodine therapy, some patients were refractory to radioactive iodine therapy and were easy to metastasize, which results in a higher mortality rate [3]. With the rapid development of molecular biology and genetic engineering, gene therapy has become a novel therapeutic strategy for TC treatment [4][5][6]. Thus, a detailed understanding of the molecular mechanism that drives TC aggravation has considerable significance for seeking a novel therapeutic target for TC.

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“…FOXN3 has been demonstrated to regulate the TGF-β/SMAD signaling pathway, which modulates the proliferation and differentiation of cancer cells (33). Overexpression of FOXN3 significantly inhibits tumor growth of papillary thyroid carcinoma, accompanied by decreased expression of the β-catenin pathway (12). Furthermore, FOXN3 may interact with β-catenin and block the interaction between β-catenin and TCF4 in colon cancer (16).…”

Section: Discussionmentioning

confidence: 99%

“…It has been demonstrated that the EMT factor, ZEB1, is transcriptionally regulated by the β-catenin/TCF4 complex pathway (11). Recently, it was reported that Forkhead box N3 (FOXN3) may interact with β-catenin and suppress the activity of the Wnt/β-catenin pathway (12). Prediction analysis using TargetScan 7.2 software (http://www.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‑182 promotes epithelial‑mesenchymal transition by targeting FOXN3 in gallbladder cancer

Zhang

Hu²,

Wen

et al. 2021

Oncol Lett

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Increasing evidence has suggested an association between the expression profiles of microRNAs (miRs) and gallbladder cancer (GBC). Recently, miR-182 has been demonstrated to exert tumor-promoting effects. However, the biological activity and molecular mechanisms of miR-182 in GBC remain unclear. The results of the present study demonstrated that miR-182 expression was significantly upregulated in GBC tissues and cell lines (GBC-SD and SGC-996). In addition, miR-182-knockdown attenuated epithelial-mesenchymal transition (EMT) in GBC cells, as indicated by decreased cell migratory and invasive abilities, decreased vimentin expression, and increased E-cadherin expression. The activities of β-catenin and its downstream factors, Cyclin D1 and c-Myc, were also demonstrated to decrease following miR-182-knockdown. Forkhead box N3 (FOXN3) was identified as the direct target of miR-182. Overexpression of FOXN3 ameliorated EMT and the β-catenin pathway. Taken together, the results of the present study suggested that miR-182 promotes EMT in GBC cells by targeting FOXN3, which suppresses the Wnt/β-catenin pathway.

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FOXN3 suppresses the growth and invasion of papillary thyroid cancer through the inactivation of Wnt/β-catenin pathway

Cited by 19 publications

References 32 publications

FOXN3 inhibits cell proliferation and invasion via modulating the AKT/MDM2/p53 axis in human glioma

FOXN3 inhibits cell proliferation and invasion via modulating the AKT/MDM2/p53 axis in human glioma

Silencing of AHNAK2 restricts thyroid carcinoma progression by inhibiting the Wnt/β-catenin pathway

MicroRNA‑182 promotes epithelial‑mesenchymal transition by targeting FOXN3 in gallbladder cancer

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