DACH1 inhibits the proliferation and migration of papillary thyroid carcinoma

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.

The cell fate regulator DACH1 modulates ferroptosis through affecting P53/SLC25A37 signaling in fibrotic disease

“…Several studies showed that DACH1 plays a significant role in the regulation of cell fate. 14 , 15 Could DACH1 be involved in the regulation of ferroptosis? To address this possibility, we first evaluated DACH1 mRNA and protein expression during HSC ferroptosis.…”

“…Dachshund homolog 1 (DACH1) is recognized as a crucial cell fate determination factor that regulates many important cellular life activities. 14 , 15 DACH1 was reported to induce cell apoptosis and arrest the cell cycle in the G2/M phase by upregulating p53 expression in HCC. 14 Moreover, DACH1 was showed to inhibit the proliferation and migration of papillary thyroid carcinoma via interacting with various cytokines such as C-X-C motif ligand8 and C-X-C motif ligand12.…”

“… 14 Moreover, DACH1 was showed to inhibit the proliferation and migration of papillary thyroid carcinoma via interacting with various cytokines such as C-X-C motif ligand8 and C-X-C motif ligand12. 15 Noteworthy, ferroptosis acts as a cell death modality that is characterized by the iron-dependent accumulation of lipid peroxidation, but whether DACH1 participates in regulating ferroptosis has not been reported. Importantly, many studies found abnormal expression of DACH1 in various fibrotic diseases, suggesting that DACH1 may be involved in the occurrence and development of fibrotic diseases.…”