Glypican 2 regulates cell proliferation and metastasis in thyroid cancer cells

Context: ZIC1 has been reported to be overexpressed and plays an oncogenic role in some brain tumors, whereas it is inactivated by promoter hypermethylation and acts as a tumor suppressor in gastric and colorectal cancers. However, until now, its biological role in thyroid cancer remains totally unknown. Objectives: The aim of this study is to explore the biological functions and related molecular mechanism of ZIC1 in thyroid carcinogenesis. Setting and Design: Quantitative RT-PCR (qRT-PCR) was performed to evaluate mRNA expression of investigated genes. Methylation-specific PCR was used to analyze promoter methylation of the ZIC1 gene. The functions of ectopic ZIC1 expression in thyroid cancer cells were determined by cell proliferation and colony formation, cell cycle and apoptosis, as well as cell migration and invasion assays. Results: ZIC1 was frequently down-regulated by promoter hypermethylation in both primary thyroid cancer tissues and thyroid cancer cell lines. Moreover, our data showed that ZIC1 hypermethylation was significantly associated with lymph node metastasis in patients with papillary thyroid cancer. Notably, restoration of ZIC1 expression in thyroid cancer cells dramatically inhibited cell proliferation, colony formation, migration and invasion, and induced cell cycle arrest and apoptosis by blocking the activities of the phosphatidylinositol-3-kinase (PI3K)/Akt and RAS/RAF/MEK/ERK (MAPK) pathways, and enhancing FOXO3a transcriptional activity. Conclusions: Our data demonstrate that ZIC1 is frequently inactivated by promoter hypermethyaltion and functions as a tumor suppressor in thyroid cancer through modulating PI3K/Akt and MAPK signaling pathways and transcription factor FOXO3a.

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Protein Kinase A-Independent Inhibition of Proliferation and Induction of Apoptosis in Human Thyroid Cancer Cells by 8-Cl-Adenosine

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2007-2331 ◽

2008 ◽

Vol 93 (3) ◽

pp. 1020-1029 ◽

Cited By ~ 15

Author(s):

Audrey J. Robinson-White ◽

Hui-Pin Hsiao ◽

Wolfgang W. Leitner ◽

Elizabeth Greene ◽

Andrew Bauer ◽

...

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Thyroid Cancer ◽

Protein Kinase ◽

Protein Kinase A ◽

Cancer Cells ◽

Human Thyroid ◽

Inhibition Of Proliferation ◽

Thyroid Cancer Cells ◽

Kinase A

Abstract Purpose: Protein kinase A (PKA) affects cell proliferation in many cell types and is a potential target for cancer treatment. PKA activity is stimulated by cAMP and cAMP analogs. One such substance, 8-Cl-cAMP, and its metabolite 8-Cl-adenosine (8-Cl-ADO) are known inhibitors of cancer cell proliferation; however, their mechanism of action is controversial. We have investigated the antiproliferative effects of 8-Cl-cAMP and 8-CL-ADO on human thyroid cancer cells and determined PKA’s involvement. Experimental Design: We employed proliferation and apoptosis assays and PKA activity and cell cycle analysis to understand the effect of 8-Cl-ADO and 8-Cl-cAMP on human thyroid cancer and HeLa cell lines. Results: 8-Cl-ADO inhibited proliferation of all cells, an effect that lasted for at least 4 d. Proliferation was also inhibited by 8-Cl-cAMP, but this inhibition was reduced by 3-isobutyl-1-methylxanthine; both drugs stimulated apoptosis, and 3-isobutyl-1-methylxanthine drastically reduced 8-Cl-cAMP-induced cell death. 8-Cl-ADO induced cell accumulation in G1/S or G2/M cell cycle phases and differentially altered PKA activity and subunit levels. PKA stimulation or inhibition and adenosine receptor agonists or antagonists did not significantly affect proliferation. Conclusions: 8-Cl-ADO and 8-Cl-cAMP inhibit proliferation, induce cell cycle phase accumulation, and stimulate apoptosis in thyroid cancer cells. The effect of 8-Cl-cAMP is likely due to its metabolite 8-Cl-ADO, and PKA does not appear to have direct involvement in the inhibition of proliferation by 8-Cl-ADO. 8-Cl-ADO may be a useful therapeutic agent to be explored in aggressive thyroid cancer.

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The Akt inhibitor KP372-1 suppresses Akt activity and cell proliferation and induces apoptosis in thyroid cancer cells

British Journal of Cancer ◽

10.1038/sj.bjc.6602595 ◽

2005 ◽

Vol 92 (10) ◽

pp. 1899-1905 ◽

Cited By ~ 65

Author(s):

M Mandal ◽

S Kim ◽

M N Younes ◽

S A Jasser ◽

A K El-Naggar ◽

...

Keyword(s):

Cell Proliferation ◽

Thyroid Cancer ◽

Cancer Cells ◽

Akt Inhibitor ◽

Thyroid Cancer Cells

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Long non-coding RNA DIO3OS/let-7d/NF-κB2 axis regulates cells proliferation and metastasis of thyroid cancer cells

Journal of Cell Communication and Signaling ◽

10.1007/s12079-020-00589-w ◽

2020 ◽

Author(s):

Mingming Wang ◽

Jin Li ◽

Zhongkun Zuo ◽

Chutong Ren ◽

Tenglong Tang ◽

...

Keyword(s):

Thyroid Cancer ◽

Cancer Cells ◽

Non Coding Rna ◽

Proliferation And Metastasis ◽

Long Non Coding Rna ◽

Thyroid Cancer Cells

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miR-9-5p Increases Sensitivity to Cisplatin in Thyroid Cancer Cells by Down-Regulating BRAF Expression

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2019.2054 ◽

2019 ◽

Vol 9 (6) ◽

pp. 751-759

Author(s):

Wanzhi Chen ◽

Jichun Yu ◽

Rong Xie ◽

Meijun Zhong

Keyword(s):

Cell Proliferation ◽

Wound Healing ◽

Thyroid Cancer ◽

Cancer Cells ◽

Cell Apoptosis ◽

Cell Number ◽

Luciferase Reporter ◽

Reporter Assay ◽

Thyroid Cancer Cells ◽

Dual Luciferase Reporter Assay

Objective: To explore the expression of miR-9-5p and BRAF in cisplatin resistant strain thyroid cancer cells and reversal effect of drug resistance as well as the possible mechanism. Methods: The cisplatin-resistant thyroid cancer cells (FTC-133/DDP and TPC-1/DDP) were respectively divided into 3 groups as NC, DDP and DDP + miRNA groups. Measuring cell proliferation by MTT assay and cell apoptosis by flow cytometry; Evaluating invasion cell number and wound healing rates by transwell and wound healing assay. The relative proteins (BRAF, Mek and Erk1/2) were measured by WB assay. The correlation between miR-9-5p and BRAF by dual-luciferase reporter assay in FTC-133/DDP and TPC-1/DDP cells. Results: In FTC-133/DDP and TPC-1/DDP cells experiment, compared with DDP group, with miR-9-5p supplement, the cell proliferation rats were significantly depressed with cell apoptosis increasing (P < 0.001, respectively); invasion cell number and wound healing rats were significantly down-regulation (P < 0.001, respectively) in DDP + miRNA groups. Meanwhile, the BRAF, Mek and Erk1/2 proteins expressions were significantly depressed in DDP + miRNA groups were significantly suppressed compared with those in DDP groups (P < 0.001, respectively). By dual-luciferase reporter assay, BRAF was the target gene of miR-9-5p in FTC133/DDP and TPC-1/DDP cells. Conclusion: miR-9-5p increases sensitivity to cisplatin in thyroid cancer cells by down-regulating BRAF expression.

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