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.

Central lymph node metastasis (CLNM) is common in papillary thyroid carcinoma (PTC). Prophylactic central lymph node dissection (PCLND) for patients with clinically negative central compartment lymph nodes (CN0) remains controversial. The phrase “clinically negative” is used to indicate that patients exhibited no clinical evidence of CLNM by ultrasonography (US) or computerized tomography (CT) preoperatively. In this study, we analyze the risk factors for CLNM in CN0 patients. The PUBMED and SCIE databases were systematically searched for works published through January 31, 2015. All of the patients included in this study underwent thyroidectomy+PCLND. Revman 5.3 software was used to analyze the data. Twenty studies and 9084 patients were included in this meta-analysis. The following variables were associated with an increased risk of CLNM in CN0 patients: age < 45 years (OR = 1.59, 95% CI = 1.42–1.78, p<0.00001), male sex (OR = 1.95, 95% CI = 1.63–2.32, p<0.00001), multifocality (OR = 1.43, 95% CI = 1.22–1.67, p 2 cm for PTC patients (OR = 2.98, 95% CI 2.08–4.28, p 0.5 cm for papillary thyroid microcarcinoma (PTMC) patients (OR = 2.30, 95% CI = 1.71–3.09, p<0.00001), location of the primary tumor in the central area and low pole (OR = 1.86, 95% CI = 1.48–2.33, p<0.00001), lymphovascular invasion (OR = 4.35, 95% CI = 2.24–8.46, p<0.0001), extrathyroidal extension (OR = 2.27, 95% CI = 1.76–2.94, p<0.00001), and capsular invasion (OR = 1.72, 95% CI = 1.39–2.41, p1cm) exhibited a higher risk factor associated with CLNM than PTMC (tumor size<1cm) (OR = 2.83, 95% CI = 2.15–3.72, p<0.00001). Bilateral tumors (OR = 1.21, 95% CI = 0.92–1.58, p = 0.17) and lymphocytic thyroiditis (OR = 0.88, 95% CI = 0.71–1.09, p = 0.25) had no association with CLNM in CN0 patients. Our systematic review identified several clinical features associated with CLNM in CN0 patients, including age, sex, multifocality, size, location, lymphovascular invasion, capsular invasion, and extrathyroidal extension. These factors should guide the application of PCLND in CN0 patients.

Background: Post-thyroidectomy haemorrhage is a rare but potentially life-threatening and unpredictable complication of thyroid surgery. In this study, we analysed the potential risk factors for the occurrence of post-thyroidectomy haemorrhage.Methods: The PubMed and SCIE databases were comprehensively searched for studies published before June 30, 2016. Studies on patients who underwent an open thyroidectomy with or without neck dissection were included, and RevMan 5.3 software was used to analyse the data.Results: Twenty-five studies and 424 563 patients were included in this meta-analysis, and post-thyroidectomy haemorrhage occurred in 6277 patients (incidence rate = 1.48%). The following variables were associated with an increased risk of post-thyroidectomy haemorrhage: older age (MD = 4.30, 95% CI = 3.09–5.52,P < 0.00001), male sex (OR = 1.73, 95% CI = 1.54–1.94,P < 0.00001), Graves’ disease (OR = 1.76, 95% CI = 1.44–2.15,P < 0.00001), antithrombotic agents use (OR = 1.96, 95% CI 1.55–2.49,P < 0.00001), bilateral operation (OR = 1.71, 95% CI = 1.50–1.96,P < 0.00001), neck dissection (OR = 1.53, 95% CI = 1.11–2.11,P = 0.01) and previous thyroid surgery (OR = 1.62, 95% CI = 1.12–2.34,P = 0.01). Malignant tumours (OR = 1.07, 95% CI = 0.89–1.28,P = 0.46) and drainage device use (OR = 1.27, 95% CI = 0.74–2.18,P = 0.4) were not associated with post-thyroidectomy haemorrhage.Conclusion: Our systematic review identified a number of risk factors for post-thyroidectomy haemorrhage, including older age, male sex, Graves’ disease, antithrombotic agents use, bilateral operation, neck dissection and previous thyroid surgery. Early control of modifiable risk factors could improve patient outcomes and satisfaction.

Nuclear paraspeckle assembly transcript 1 (NEAT1), a long non-coding RNA (lncRNA), is a core structural component of paraspeckles and is essential for paraspeckle formation. NEAT1 comprises two different isoforms: NEAT1_1 (3.7 kb) and NEAT1_2 (23 kb). Recently, NEAT1 has been shown to have oncogenic roles and to facilitate tumorigenesis in various human cancers. However, the function of NEAT1 in papillary thyroid cancer (PTC) is not well understood. The relative expression levels of NEAT1_2, ATPase family AAA domain-containing protein 2 (ATAD2), and microRNA-106b-5p (miR-106b-5p) were assessed via quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Four PTC cell lines were used to detect the relative expression of NEAT1_2. The effects of NEAT1_2 on PTC cells were studied by RNA interference approaches in vitro. The effects of NEAT1_2 on downstream proteins were detected by western blotting. The underlying mechanism was clarified by a rescue experiment, and three dual-luciferase reporter assays. NEAT1_2 expression was markedly increased in PTC tissues and the PTC cell lines (K1 and TPC1). The relative expression level of NEAT1_2 was positively associated with TNM stage and tumor size. NEAT1_2 knockdown led to a significant inhibition of growth and metastasis, and induced apoptosis in PTC cells. Knockdown of NEAT1_2 significantly inhibited malignant biological behavior by downregulating the oncogene ATAD2. In addition, NEAT1_2 could act as a competing endogenous RNA to regulate the expression of ATAD2 through downregulating miR-106b-5p. Taken together, our results indicated that NEAT1_2 is overexpressed in PTC. NEAT1_2 could function as a competing endogenous RNA to regulate ATAD2 expression by sponging miR-106b-5p in PTC. Targeting NEAT1_2 could be a promising therapeutic strategy for patients with PTC.

Background: As hypocalcemia is the most common complication of total thyroidectomy, identifying its risk factors should guide prevention and management. The purpose of this study was to determine the risk factors for postthyroidectomy hypocalcemia.Methods: We searched PubMed, Web of Science and EMBASE through January 31, 2019, and assessed study quality using the Newcastle–Ottawa Scale.Results: Fifty studies with 22,940 patients met the inclusion criteria, of which 24.92% (5716/22,940) had transient hypocalcemia and 1.96% (232/11,808) had permanent hypocalcemia. Significant (P < 0.05) predictors of transient hypocalcemia were: younger age, female, parathyroid autotransplantation (PA), inadvertent parathyroid excision (IPE), Graves’ disease (GD), thyroid cancer, central lymph node dissection, preoperative severe Vitamin D deficiency, preoperative Vitamin D deficiency and a lower postoperative 24 h parathyroid hormone (PTH) level. Preoperative magnesium, preoperative PTH and Hashimoto’s thyroiditis were not significant predictors of transient hypocalcemia. IPE, GD, and thyroid cancer were associated with an increased rate of permanent hypocalcemia, but gender and PA did not predict permanent hypocalcemia.Conclusion: Important risk factors for transient and permanent hypocalcemia were identified. However, given the limited sample size and heterogeneity of this meta-analysis, further studies are required to confirm our preliminary findings.