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.

The incidence of papillary thyroid cancer (PTC) is markedly higher in women than men during the reproductive years. In vitro studies have suggested that estrogen may play an important role in the development and progression of PTC through estrogen receptors (ERs). This study aimed to investigate the expression patterns of the two main ER subtypes, α and β1 (wild-type ERβ), in PTC tissue and their clinical significance.

Estradiol (E2) promotes metastatic propensity. However, the detailed mechanism remains largely unknown. E-cadherin, vimentin, and MMP-9 play a dominant role in the metastatic process. We aimed to investigate the effects of E2 on metastatic potential of PTC cell line BCPAP and on E-cadherin, vimentin, and MMP-9 protein expression. PTC cell line BCPAP was evaluated for the presence of estrogen receptor (ER) by western blot analysis. The effects of E2, PPT (a potent ERα-selective agonist), and DPN (a potent ERβ-selective agonist) on modulation of metastatic phenotype were determined by usingin vitroscratch wound assay and invasion assay. In addition, the effects on E-cadherin, vimentin, and matrix metalloproteinase-9 (MMP-9) protein expression were evaluated by Western blot analysis. We found that BCPAP cells expressed ERαand ERβ. E2 and PPT enhanced, but DPN inhibited, the migration and invasion of BCPAP cells in anin vitroexperimental model system that is modulated by E-cadherin, vimentin, and MMP-9. These findings indicate that E2 induces the metastatic potential of BCPAP cells through ERαand ERβ. The two ER subtypes play differential roles in modulation of BCPAP cell metastasis and the related molecule expressions including E-cadherin, vimentin, and MMP-9.

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.

An increase in the prevalence of thyroid disease has been found with increasing iodine intake, since universal salt iodization (USI) was instituted throughout China in 1996. The aim of this study was to analyze the incidence of thyroid carcinoma (TC) before and after USI in Shenyang, a city of northeastern China. The pathology reports were collected from patients with thyroid diseases who underwent surgery in the First Hospital of China Medical University from January 1, 1992 to December 31, 2009. The detection rate, the constituent ratio, the changes of sex, age, and concomitant thyroid diseases of each histological type of TC were analyzed. The detection rate of TC, papillary thyroid carcinoma (PTC), and medullary thyroid carcinoma (MTC) increased; that of follicular thyroid carcinoma (FTC) decreased; and that of undifferentiated thyroid carcinoma (UTC) showed no change after USI. The constituent ratio of PTC increased, that of FTC and UTC decreased, and that of MTC showed no change after USI. The mean age of female patients with TC decreased after USI. The incidences of PTC complicated with either nodular goiter or chronic lymphocytic thyroiditis increased after USI. The detection rate of TC increased significantly, PTC predominated in the histological types of TC, and the mean age of female patients with TC decreased after USI. The patients with either nodular goiter or chronic lymphocytic thyroiditis under high iodine intake should be followed up.

Papillary thyroid carcinoma (PTC), the most common histological subtype of thyroid cancer, accounts for between 80 and 90% of all thyroid cancer cases. Previous studies have suggested that microRNAs (miRNAs/miRs) are involved in the development of PTC. The aim of the present study was to investigate whether miR‑144 inhibits cellular proliferation in PTC. The expression of miR‑144 was detected in PTC and corresponding adjacent non‑cancerous tissues, and in the PTC cell line IHH4, using reverse transcription‑quantitative polymerase chain reaction. Associations between miR‑144 expression levels and the clinicopathological characteristics were analyzed. Receiver operating characteristic (ROC) curves were used to assess the diagnostic value of miR‑144 expression, and the potential function of miR‑144 was investigated in IHH4 cells using a Cell Counting Kit‑8 and colony formation assays. Western blotting was applied to analyze the expression level of WW domain‑containing transcription regulator 1 (WWTR1) in PTC tissues. miR‑144 was significantly downregulated in PTC tissues and the PTC cell line. Low expression of miR‑144 was associated with larger tumor sizes (P<0.001). The ROC curves demonstrated that miR‑144 may be a potential biomarker for identifying PTC and non‑cancerous diseases (sensitivity, 58.7%; specificity, 87.3%) as well as to differentiate PTC with tumor sizes ≥2 cm (sensitivity, 79.2%; specificity, 69.2%). Upregulation of miR‑144 significantly suppressed proliferation in IHH4 cells. WWTR1 was overexpressed in PTC tissues compared with in adjacent non‑cancerous tissues, and the ectopic expression of miR‑144 downregulated WWTR1 in IHH4 cells. Co‑transfection with pcDNA‑WWTR1 and miR‑144 ‘rescued’ the proliferation inhibition. The results of the present study collectively demonstrated that miR‑144 is downregulated in PTC, that low expression levels of miR‑144 are associated with larger tumor sizes and that miR‑144 inhibits cellular proliferation in PTC by targeting WWTR1.