Endocrine Abstracts

Kelch-like protein 14 (KLHL14) is a member of the Kelch protein family acting as a subunit of E3-ubiquitin ligase. KLHL14 and its antisense lncRNA, KLHL14-AS, are among the most enriched transcripts in the developing mouse thyroid. Recently, we showed that KLHL14-AS is a tumor suppressor in thyroid carcinomas (TC) involved in the maintenance of differentiation and proliferation rate of thyroid follicular cells. KLHL14 is a tumor suppressor in Diffuse Large B Cell Lymphoma, its role in TC is unknown. Herein we investigate the implication of KLHL14 in thyroid cells differentiation also exploiting mice thyroid organoids. qPCR analysis highlighted a positive correlation between the two genes in many human TC cell lines of different histological subtypes, with their gradual downregulation being correlated to cancer progression, thus to cells differentiation. Moreover, the rescue of KLHL14 by transfection in anaplastic TC cells, in which it is normally absent, enhances the transcription of many specific markers, such as Thyroglobulin, NKX2-1 and FOXE1. Finally, RNA expression analyses on mice-derived thyroid organoids revealed that KLHL14 levels increase in several conditions which promote cells differentiation, i.e. media-induced differentiation or photon irradiation. Our findings reveal that KLHL14, as previously demonstrated for its antisense, seems to be involved in thyroid cells differentiation. Incoming studies with mice-derived thyroid organoids model will clarify the importance of KLHL14 in this process and also in TC differential diagnosis or drug-response prediction.