HSPA5-associated transcriptional programs and cellular phenotypes in follicular thyroid carcinoma
Year: 2026
Type: article
Abstract: Background Follicular thyroid carcinoma (FTC) is difficult to distinguish from benign follicular lesions before surgery. This study examined heat shock protein family A member 5 (HSPA5), an endoplasmic reticulum chaperone, and its association with ferroptosis-related transcriptional programs and cellular phenotypes in FTC. Methods Five public transcriptomic cohorts were integrated for candidate discovery, external characterization, and paired-tissue evaluation. HSPA5 was silenced with two short-hairpin RNA constructs in FTC-238 and FTC-133 cells. Knockdown, metabolic activity, DNA synthesis, wound closure, migration, and invasion were evaluated using molecular and cell-based assays. Results In exploratory analyses, HSPA5 correlated with ferroptosis-driver and lipid-peroxidation scores (Spearman rho = 0.709 and 0.791; false-discovery rates = 0.023 and 0.013). Expression was higher in eight patient-matched primary FTC samples than in adjacent thyroid ( P = 0.0078). External discrimination between FTC and follicular adenoma was limited (area under the receiver-operating-characteristic curve = 0.51). In both FTC-238 and FTC-133 cells, HSPA5 silencing reduced the 24-h Cell Counting Kit-8 (CCK-8) signal and the numbers of migrating and invading cells, but increased the 5-ethynyl-2'-deoxyuridine (EdU)-positive fraction. Conclusion HSPA5 is associated with ferroptosis-related transcriptional programs, and its depletion reduces 24-h CCK-8 signals and Transwell cell counts in FTC models. The role of HSPA5 in ferroptotic cell death requires functional validation.
Source: Frontiers in Medicine
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7225414643