Downregulation of FAM134B suppresses thyroid cell carcinoma development by modulating endoplasmic reticulum stress and autophagy.

This study investigated the molecular mechanism by which FAM134B regulates endoplasmic reticulum stress (ERS) and autophagy to promote thyroid carcinoma (THCA) development. FAM134B expression in clinical THCA samples was examined. FAM134B expression was knocked down in TPC-1 cells, while FAM134B was overexpressed in KTC-1 cells. Cell proliferation and apoptosis were determined. Cleaved caspase-3 (C-Casp-3), caspase-12, and unfolded protein response markers were detected. LC3B fluorescence expression and Calnexin-LAMP1 co-localization were assessed. FAM134B was highly expressed in THCA, and its overexpression was significantly associated with higher T staging. Knocking down FAM134B reduced THCA cell proliferation and encouraged apoptosis, while its overexpression resulted in contrary effects. FAM134B knockdown activated ERS (upregulating p-PERK/PERK, p-IRE1α/IRE1α, and CHOP) and enhanced autophagy (increasing LC3-II/I expression levels, decreasing p62 expression levels, and enhancing Calnexin-LAMP1 colocalization). Inhibition of ERS partially reversed the suppression of malignant biological behavior in THCA cells caused by FAM134B knockdown. FAM134B acts as an oncogene in THCA. Silencing FAM134B inhibits THCA cell proliferation and promotes apoptosis by inducing ERS and autophagy.