PDE4C stabilized by ELAVL1 promotes lymph node metastasis in papillary thyroid cancer

Lymph node metastasis (LNM) is a key factor in the recurrence and progression of papillary thyroid carcinoma (PTC).Phosphodiesterase 4C (PDE4C) serves as a crucial regulator in cancer development and metastasis, its functional role and mechanism in LNM of PTC need further elucidation.PDE4C and embryonic lethal abnormal vision like 1 (ELAVL1) expression in PTC and adjacent normal tissues were assessed using bioinformatic analysis and immunohistochemistry (IHC).We found that PDE4C and ELAVL1 were upregulated in PTC tissues.Cell viability in BCPAP and TPC-1 cell lines was assessed via cell counting kit-8 (CCK-8) assay, while Transwell assays were employed to determine their migratory and invasive capacities.Our data revealed that silencing of PDE4C remarkably suppressed BCPAP and TPC-1 cell proliferation, migration and invasion.Besides, the association between ELAVL1 and PDE4C was predicted and verified by ENCORI, RNA pull down and RNA immunoprecipitation (RIP) assay.The mRNA of ELAVL1 and PDE4C were evaluated via quantitative real-time PCR (qRT-PCR).ELAVL1 and PDE4C expression was examined using Western blot analysis.The number of metastatic tumors in the lymph nodes was assessed by hematoxylin-eosin (HE) staining.Ki-67 level in tumor tissues were determined by IHC.ELAVL1 interacts with PDE4C, resulting in an increase in PDE4C mRNA stability, which contributes to the aforementioned malignant phenotypes.Consistently, the knockdown of PDE4C or ELAVL1 inhibited LNM of PTC cells, PTC growth, and Ki-67 expression in vivo.In summary, ELAVL1 promotes LNM in PTC by stabilising PDE4C.Our study elucidates the molecular mechanisms driving PTC metastasis, offering new therapeutic avenues for PTC treatment.