We previously identified that the expression of chitinase‐3‐like protein 1 (CHI3L1) was upregulated during thyroid cancer progression. Here, we investigated the prognostic significance of CHI3L1 expression in thyroid neoplasms and examined the potential oncogenic roles. CHI3L1 immunochemical staining was performed on tissue microarrays of benign and malignant thyroid tumours. Compared with normal thyroid tissue and benign thyroid lesions that had low or no detectable CHI3L1 expression, CHI3L1 was overexpressed in both differentiated and undifferentiated thyroid cancer. High CHI3L1 expression was associated with extrathyroidal extension, lymph node metastasis, and shorter recurrence‐free survival in differentiated thyroid cancer. The biological roles of CHI3L1 were further investigated by gain‐ and loss‐of‐function assays. CHI3L1 silencing suppressed clonogenicity, migration, invasion, anoikis resistance, and angiogenesis in thyroid cancer cells, although exogenous CHI3L1 treatment promoted these malignant phenotypes. Cysteine‐rich angiogenic inducer 61 (CYR61) was identified as a downstream target of CHI3L1 by RNA‐seq analysis. CYR61 silencing or treatment reversed the alterations induced by CHI3L1 modulation. Our results demonstrate that CHI3L1 is overexpressed in thyroid cancer and is associated with an increased risk of disease recurrence. Additionally, CYR61 may participate in CHI3L1‐mediated tumour progression. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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Cellular retinoic acid-binding protein 2 (CRABP2) participates in retinoid partitioning between different nuclear receptors. Recently, we identified that CRABP2 is one of the progression-associated genes in thyroid cancer. To explore the prognostic and functional significance of CRABP2, immunohistochemical analysis was performed in thyroid tissues and neoplasms. Overexpression of CRABP2 was observed in malignant thyroid neoplasms but not in benign thyroid lesions. CRABP2 expression was an independent predictive factor for recurrence-free survival in patients with differentiated thyroid cancer. Knockdown of CRABP2 reduced the sensitivity of thyroid cancer cells to retinoic acid. Importantly, CRABP2 expression in thyroid cancer cells was associated with epithelial-mesenchymal transition properties, including anoikis resistance, migration, and invasion capacity. Furthermore, invasion promoted by CRABP2 was mediated at least partly by the integrin/FAK/AKT pathway. In summary, CRABP2 expression is upregulated in thyroid cancer with adverse prognostic implications. The invasion-stimulating effects appear independent of canonical retinoic acid signaling and may serve as a potential therapeutic target.

Background/Aim: Ethacridine is used as a topical antiseptic as well as for second-trimester abortion. Recent studies showed that ethacridine is an inhibitor of poly(ADPribose) glycohydrolase (PARG) and an activator of the transcriptional coactivator with PDZ-binding motif (TAZ). This study examined the effects of ethacridine on thyroid cancer cells. Materials and Methods: Thyroid cancer cell lines (FTC133 and SW1736) and thyroid follicular epithelial cells (Nthy-ori 3-1) were treated with ethacridine. Viability, clonogenicity, cell-cycle distribution, and apoptosis were evaluated. The expression of thyroid differentiation markers (TTF-1, PAX8, and NIS) was determined by real-time PCR. Results: Ethacridine suppressed cell growth and clonogenic ability of thyroid cancer cells in a time-and dose-dependent manner (p<0.001). No cell-cycle arrest was found, but ethacridine dose-dependently induced apoptosis of thyroid cancer cells (p<0.001). The PAX8 and NIS expressions were significantly increased in SW1736 (3.41-fold and 1.53-fold, respectively) and respectively). Conclusion: Ethacridine elicits apoptotic cell death in thyroid cancer cells and promotes differentiation in a subset of thyroid follicular cells.