Abstract

Papillary thyroid carcinoma (PTC) is the most prevalent subtype of thyroid cancer; however, the regulatory mechanisms by which mitophagy influences its progression remain inadequately elucidated. This study sought to examine the role of myoferlin (MYOF) in mitophagy and its molecular basis during PTC development. Utilizing three paired PTC and adjacent normal tissues, we observed elevated MYOF expression at both protein and mRNA levels through western blot and qRT-PCR analyses. Stable MYOF knockdown cell lines were established in PTC (TPC-1, KTC-1) and normal thyroid (Nthy-ori 3-1) cells using lentiviral shRNA. Functional assays, including CCK-8, wound healing, transwell, flow cytometry, immunofluorescence, and mitophagic flux analysis, along with a xenograft mouse model, were employed. Subsequent evaluations involved hematoxylin and eosin staining, immunohistochemistry, western blot, and qRT-PCR. As a result, MYOF was significantly upregulated in PTC tissues and TPC-1 cells. Knockdown of MYOF inhibited PTC cell proliferation, invasion, migration, and colony formation, while promoting apoptosis. Mechanistically, MYOF was found to regulate PTC progression through the PINK1/Parkin-mediated mitophagy pathway. In vivo xenograft experiments demonstrated that MYOF silencing suppressed tumor growth and increased the expression of mitophagy-related proteins BNIP3 and NIX. In conclusion, MYOF drives PTC progression by repressing mitophagy. Targeted inhibition of MYOF activates tumor-suppressive mitophagy via the PINK1-Parkin axis, indicating MYOF as a potential therapeutic target in PTC.