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Published on: August 23, 2019
DACH1 inhibits the proliferation and migration of papillary thyroid carcinoma
Shengru Liang1,2, Qian Xu1, Boyun Liu3
1Department of Endocrinology, Xijing Hospital, Air Force Medical University, Xi'an, China.
Abstract:
DACH1 is an important component of the retinal determinate gene network (RDGN), which regulates the expression of target genes by directly binding or interacting with other factors. DACH1 shows inhibitory effects in most tumors, but its role in papillary thyroid carcinoma is unclear and warrants further investigation. We assessed the expression of DACH1 in different tissues and correlation with immune infiltration by The Cancer Genome Atlas (TCGA) and Tumor Immune Estimation Resource (TIMMER2.0 databases). The effects of DACH1 on the proliferation and migration of TPC-1 and Bcpap cells were assessed by cell viability assay, colony formation assay, wound healing assay, transwell migration assay, and flow cytometry. Finally, the effects of DACH1 on CXCL8, CXCL10, and CXCL12 expression in Nthy-ori-3-1, TPC-1 and Bcpap cells were assessed by enzyme-linked immunosorbent assay kit and real-time polymerase chain reaction, respectively. The results showed that DACH1 was differentially expressed in different tumors and tissues. Basal expression of DACH1 was lower in thyroid and papillary thyroid carcinoma than in other normal tissues and corresponding tumors, and positively correlated with CD8+ T cell infiltration. In Nthy-ori-3-1, TPC-1 and Bcpap cells, overexpression of DACH1 inhibited cell migration and proliferation, and the opposite results was obtained by knocking down DACH1 using small interfering RNA. We also demonstrated that DACH1 regulated chemokines CXCL8, CXCL10, and CXCL12, thereby modulating tumor immunity.
Insights
DACH1, a gene regulating cell growth, is downregulated in papillary thyroid carcinoma and inhibits tumor cell proliferation and migration. Its expression correlates with immune cell infiltration, suggesting a role in modulating tumor immunity.
Area of Science:
- Molecular Biology
- Oncology
- Immunology
Background:
- DACH1 is part of the retinal determinate gene network (RDGN), regulating gene expression.
- DACH1 typically inhibits tumor growth, but its function in papillary thyroid carcinoma (PTC) is not well understood.
Purpose of the Study:
- To investigate the expression of DACH1 in thyroid tissues and its correlation with immune infiltration.
- To determine the functional role of DACH1 in papillary thyroid carcinoma cell proliferation and migration.
- To explore DACH1's effect on chemokine expression and tumor immunity.
Main Methods:
- Utilized The Cancer Genome Atlas (TCGA) and Tumor Immune Estimation Resource (TIMER2.0) databases for expression and immune infiltration analysis.
- Employed cell viability, colony formation, wound healing, transwell migration, and flow cytometry assays to assess DACH1's impact on cell behavior.
- Measured CXCL8, CXCL10, and CXCL12 expression using ELISA and real-time PCR.
Main Results:
- DACH1 expression was lower in thyroid cancer tissues compared to normal tissues and positively correlated with CD8+ T cell infiltration.
- Overexpression of DACH1 suppressed proliferation and migration in TPC-1 and Bcpap cells, while knockdown enhanced these processes.
- DACH1 was found to regulate the expression of chemokines CXCL8, CXCL10, and CXCL12.
Conclusions:
- DACH1 plays an inhibitory role in papillary thyroid carcinoma progression.
- DACH1 influences tumor immunity by modulating chemokine expression and immune cell infiltration.
- DACH1 represents a potential therapeutic target for papillary thyroid carcinoma.
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