Background: N6-methyladenosine (m⁶A) modification is the most common chemical modification in mammalian mRNAs, and it plays important roles by regulating several cellular processes. Previous studies report that m⁶A is implicated in modulating tumorigenesis and progression. However, dysregulation of m⁶A modification and effect of m⁶A demethylase fat-mass and obesity-associated protein (FTO) on glucose metabolism has not been fully elucidated in papillary thyroid cancer (PTC). Methods: Quantitative real-time PCR (qRT-PCR), western blotting and immunohistochemistry were performed to explore the expression profile of FTO in PTC tissues and adjacent non-cancerous thyroid tissues. Effects of FTO on PTC glycolysis and growth were investigated through in vitro and in vivo experiments. Mechanism of FTO-mediated m⁶A modification was explored through transcriptome-sequencing (RNA-seq), methylated RNA immunoprecipitation sequencing (MeRIP-seq), MeRIP-qPCR, luciferase reporter assays, RNA stability assay and RNA immunoprecipitation assay. Results: FTO expression was significantly downregulated in PTC tissues. Functional analysis showed that FTO inhibited PTC glycolysis and growth. Further analyses were conducted to explore FTO-mediated m⁶A modification profile in PTC cells and Apolipoprotein E (APOE) was identified as the target gene for FTO-mediated m⁶A modification using RNA-seq and MeRIP-seq. FTO knockdown significantly increased APOE mRNA m⁶A modification and upregulated its expression. FTO-mediated m⁶A modification of APOE mRNA was recognized and stabilized by the m⁶A reader IGF2BP2. The findings showed that APOE also promoted tumor growth through glycolysis in PTC. Analysis showed that FTO/APOE axis inhibits PTC glycolysis by modulating IL-6/JAK2/STAT3 signaling pathway. Conclusion: FTO acts as a tumor suppressor to inhibit tumor glycolysis in PTC. The findings of the current study showed that FTO inhibited expression of APOE through IGF2BP2-mediated m⁶A modification and may inhibit glycolytic metabolism in PTC by modulating IL-6/JAK2/STAT3 signaling pathway, thus abrogating tumor growth.

Long non-coding RNAs (lncRNAs) are emerging regulators of a diverse range of biological processes through various mechanisms. Genome-wide association studies of tumor samples have identified several lncRNAs, which act as either oncogenes or tumor suppressors in various types of cancers. Small nucleolar RNAs (snoRNAs) are predominantly found in the nucleolus and function as guide RNAs for the processing of transcription. As the host genes of snoRNAs, lncRNA small nucleolar RNA host genes (SNHGs) have been shown to be abnormally expressed in multiple cancers and can participate in cell proliferation, tumor progression, metastasis, and chemoresistance. Here, we review the biological functions and emerging mechanisms of SNHGs involved in the development and progression of endocrine-related cancers including thyroid cancer, breast cancer, pancreatic cancer, ovarian cancer and prostate cancer.

Metastases to the thyroid gland arise from other malignant tumors such as renal cell carcinoma, colorectal cancer, lung cancer, and breast cancer. In clinical practice, the incidence is low, and the symptoms are not specific, so it is often missed and misdiagnosed. It is finally diagnosed via the comprehensive application of many diagnostic methods, such as ultrasound, fine-needle aspiration biopsy, and immunohistochemistry analysis. Surgery-based comprehensive treatment is often adopted, but because it is usually in the late stage of the primary tumor, the prognosis is poor. In order to better understand the related characteristics of thyroid metastatic cancer and then improve the clinical diagnosis and treatment and the prognosis of patients, in this paper, we systematically summarize the research status of thyroid metastatic cancer.

Pediatric papillary thyroid carcinomas (PPTCs) exhibit high inter-tumor heterogeneity and currently lack widely adopted recurrence risk stratification criteria. Hence, we propose a machine learning-based objective method to individually predict their recurrence risk. We retrospectively collect and evaluate the clinical factors and proteomes of 83 pediatric benign (PB), 85 pediatric malignant (PM) and 66 adult malignant (AM) nodules, and quantify 10,426 proteins by mass spectrometry. We find 243 and 121 significantly dysregulated proteins from PM vs. PB and PM vs. AM, respectively. Function and pathway analyses show the enhanced activation of the inflammatory and immune system in PM patients compared with the others. Nineteen proteins are selected to predict recurrence using a machine learning model with an accuracy of 88.24%. Our study generates a protein-based personalized prognostic prediction model that can stratify PPTC patients into high- or low-recurrence risk groups, providing a reference for clinical decision-making and individualized treatment.