Related Experiment Video
Updated: May 1, 2026

In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
ZIC1 is a putative tumor suppressor in thyroid cancer by modulating major signaling pathways and transcription factor
Wei Qiang1, Yuan Zhao, Qi Yang
1Department of Endocrinology (W.Q., Q.Y., W.L., S.L., B.S., P.H.), The First Affiliated Hospital of Xi'an Jiaotong University School of Medicine, Xi'an 710061, China; Department of Gerontology (Y.Z.), Shaanxi Provincial People's Hospital, Xi'an 710068, China; Department of Endocrinology and Metabolism (H.G.), The First Affiliated Hospital of China Medical University, Shenyang 110001, China; and Center for Translational Medicine (M.J.), The First Affiliated Hospital of Xi'an Jiaotong University School of Medicine, Xi'an 710061, China.
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.
Insights
ZIC1 acts as a tumor suppressor in thyroid cancer, frequently inactivated by promoter hypermethylation. Its restoration inhibits cancer cell growth and metastasis by affecting key signaling pathways.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genetics
Background:
- ZIC1 exhibits dual roles in cancer, acting as an oncogene in brain tumors but a tumor suppressor in gastric and colorectal cancers.
- The function of ZIC1 in thyroid cancer pathogenesis was previously uncharacterized.
Purpose of the Study:
- To elucidate the biological functions of ZIC1 in thyroid carcinogenesis.
- To investigate the molecular mechanisms underlying ZIC1's role in thyroid cancer.
Main Methods:
- Quantitative RT-PCR and methylation-specific PCR were employed to assess ZIC1 expression and promoter methylation.
- Functional assays including cell proliferation, colony formation, cell cycle, apoptosis, migration, and invasion assays were conducted.
Main Results:
- ZIC1 is frequently downregulated in thyroid cancer tissues and cell lines due to promoter hypermethylation.
- ZIC1 hypermethylation correlates with lymph node metastasis in papillary thyroid cancer.
- Restoring ZIC1 expression suppressed proliferation, colony formation, migration, and invasion, while inducing cell cycle arrest and apoptosis.
Conclusions:
- ZIC1 functions as a tumor suppressor in thyroid cancer, inactivated by promoter hypermethylation.
- ZIC1 modulates the PI3K/Akt and MAPK signaling pathways.
- ZIC1 enhances FOXO3a transcriptional activity, contributing to its tumor-suppressive role.
More Related Videos
Related Concept Videos
Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Cancer-Critical Genes II: Tumor Suppressor Genes
Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
Loss of Tumor Suppressor Gene Functions
Canonical Wnt Signaling Pathway
Abnormal Proliferation

