SPSB4 as a risk factor for papillary thyroid cancer: Enhancing cell vitality under excess iodine exposure

Abstract Objective The varying environmental exposure to iodine has long been a topic of interest, particularly given the noticeable increase in the incidence of papillary thyroid carcinoma (PTC) compared to other histopathological subtypes globally. This rise in thyroid cancer incidence has been attributed to several factors, including improved detection of early tumors, a higher prevalence of modifiable individual risk factors, and differing exposure to environmental risk factors such as iodine levels. This study aims to explore the epigenetic mechanisms that promote thyroid cancer progression under excess iodine exposure. Materials and methods This study outlines the following strategy: (i) risk factors were identified through statistical analysis of questionnaire responses in a retrospective iatrogenic study; (ii) following the identification of risk factors, RNA sequencing was performed using tissues from iodine-adequate (IA) and iodine-excess (IE) regions; (iii) candidate hub genes were selected via bioinformatics analysis; (iv) molecular biological techniques were employed to verify the functionality of the key gene. Results Through careful selection, we focused on SPSB4, a ubiquitin ligase previously unreported in relation to both iodine and thyroid cancer. By optimizing the dosage of PTC cell line activities, we determined how varying iodine levels can either enhance or impair the vitality of thyroid cancer cells. As anticipated, migration and invasion assays revealed significant changes when SPSB4 function was disrupted at the critical dose of KIO3. Conclusions In terms of epigenetic alterations, SPSB4 emerges as a promising candidate for further investigation, particularly in understanding thyroid cancer progression and potential carcinogenesis. Moreover, E3 ubiquitin ligases, including SPSB4, play a role in orchestrating adipose thermogenesis to maintain body temperature during cold stimuli. This study could also shed light on the influence of iodine on thermogenesis mediated by SPSB4 under cold conditions, while suggesting future exploration of SPSB4's effects on thyroid cancer in colder regions.