Gene expression profile, and role of baicalein in the inhibition of thyroid cancer.

BACKGROUND: Anaplastic thyroid cancer (ATC) is the highly undifferentiated form of thyroid cancer, and its incidence is still high all around the globe. The current treatment for ATC includes surgery, chemotherapy, and radioactive iodine therapy. These treatment options are not reliable due to high cost, drug resistance, and toxicity issues. Baicalein (BA) is a natural flavonoid isolated from Scutellaria baicalensis that exhibits several pharmacological activities, including anticancer, anti-inflammatory, antioxidant, and antitumor. The role of BA in elucidating the mechanism of ATC, emphasizing the CLU-mediated mitophagy, remains unclear. This study was designed to investigate the impact of BA on gene expression and cellular pathways in CAL62 ATC cells by CLU-mediated mitophagy. METHODS: Differential gene expression and pathway enrichment were assessed using RNA sequencing and gene set enrichment analysis (GSEA). Mitochondrial fluorescence and mitophagy markers (PINK1, PRKN, ATG5, MFN1) were evaluated by quantitative polymerase chain reaction (qPCR) and fluorescence microscopy. CLU expression and its correlation with cancer progression were analyzed using The Cancer Genome Atlas (TCGA) data. RESULTS: BA treatment altered gene expression and pathway activity, impacting processes including cell proliferation, mitophagy, and epithelial-mesenchymal transition. It reduced the mitochondrial fluorescence intensity and mitophagy marker levels, consistent with an inhibition of mitophagy. BA also modulated thyroid cancer markers, indicating the induced dedifferentiation. TCGA analysis confirmed the CLU upregulation in thyroid cancer, linking it to disease progression and survival. BA inhibits ATC cell growth, an effect associated with the alteration of CLU-linked mitophagy and key signaling pathways. CONCLUSIONS: These findings highlight that CLU as a potential therapeutic target and suggested BA as a promising strategy for thyroid cancer intervention.