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Background: The optimal serum thyroid-stimulating hormone (TSH) level for post-lobectomy papillary thyroid carcinoma (PTC) patients is unclear. The objective of this study was to examine the association of TSH and recurrence in post-lobectomy patients. Methods: Patients who underwent lobectomy for PTC in a single tertiary hospital from January 2000 to December 2014 were enrolled. The mean TSH score of a patient was calculated based on each serum TSH value during follow-up. The TSH value of each follow-up visit was scored as 0-20 with an interval of 0.5 mU/L, and the mean TSH score (MTS) was calculated as the average of all available scores for a patient. The reference range of serum TSH was 0.5-4.0 mU/L (MTS 0-7). Univariate and multivariable analyses were performed with Cox proportional hazards models. Restricted cubic spline (RCS) functions were used to model relationships between MTS and recurrence-free survival (RFS). Results: A total of 2297 patients (median age, 42 years; 1750 (76.2%) female) were analyzed. MTS below (≤0.5), in the lower half (0.5-3), in the upper half (3-7) and above (>7) the reference range were observed in 415 (18.1%), 1376 (59.9%), 409 (17.8%), and 97 (4.2%) patients, respectively. According to the Cox model and RCS, no association was observed between MTS and RFS (adjusted P=0.5071, adjusted P for nonlinear=0.5182). The only RFS difference observed in the stratified univariate analysis was between patients with MTS in the lower half (n=793) and above the reference range (n=54) in the intermediate- to high-risk group (10-year RFS by Kaplan-Meier 82.1% vs 70.5%, log rank p=0.023). Conclusions: Mean serum TSH levels are not associated with recurrence. A normal TSH reference range is recommended for post-lobectomy PTC patients. Funding Information: The study was funded by the CAMS Innovation Fund for Medical Sciences (CIFMS) (Grant no.2016-I2m-1-002) and Beijing Hope Run Special Fund of Cancer Foundation of China (Grant no.LC2018A26) Declaration of Interests: The authors have no conflicts of interest to disclose. Ethics Approval Statement: The study was approved by the Ethics Committee of the Cancer Hospital, Chinese Academy of Medical Sciences. Informed consent was obtained at the time of surgery with surgical consent for general use of clinical information for future studies.

Endometrioid endometrial carcinoma (EEC) is one of the most common malignant gynecologic tumors worldwide. Most EEC cases are associated with activities of the mTOR pathway, which regulates protein synthesis, cell growth and autophagy. While Up-Frameshift 1(UPF1) is a key protein factor in the nonsense-mediated mRNA degradation pathway (NMD), its role in carcinogenesis of EEC remains unclear. In this study, we first evaluated the expression level of UPF1 in EEC tissues and cell lines. Then, we investigated the effect of UPF1 on cellular function and mTOR signaling pathway; these effects were further validated in vivo. Finally, its effect on autophagy was evaluated by western blot and GFP-mRFP-LC3 staining. UPF1 expression in the EEC tissue samples was significantly higher than that of matched normal tissue samples. Overexpression of UPF1 promotes migration and invasion of EEC cells. Conversely, depletion of UPF1 suppresses migration and invasion of EEC cells. In addition, overexpression of UPF1 increased the in vivo growth of our EEC xenograft tumor. Finally, UPF1 increased the activity of the mTOR/P70S6K/4EBP1 signaling pathway and inhibited autophagy in EEC cells. These findings suggest that UPF1 functions as an oncogene to promote EEC carcinogenesis. Our findings propose UPF1 as a new potential therapeutic target for EEC. Funding Statement: This study was supported by the Guangdong Science and Technology Department (No.2019A1515012194), The Health and Family Planning Commission of Guangzhou Municipality (No.201707010425)，and Lin He’s Academician Workstation of New Medicine and Clinical Translation. Declaration of Interests: The all authors declare that they have no competing interests. Ethics Approval Statement: All patients provided informed consent, and the study was approved by the ethics committee of Third Affiliated Hospital of Guangzhou Medical University.

Background: Membrane associated ring-CH-type finger (MARCH) proteins belong to E3 ubiquitin ligase family, which regulates protein stability by increasing ubiquitin. Recent evidences have shown that some of MARCH proteins play important roles in cancer development. However, it remains unknown about the role of MARCH6 in tumorigenesis, including thyroid cancer. Here we intended to investigate the significance of MARCH6 in thyroid carcinogenesis. Methods: qRT-PCR, immunoblotting and IHC were used to detect the expression of MARCH6 in thyroid cancer tissues. CCK8, colony formation, cell cycle, apoptosis, transwell and xenografted tumorigenesis assays were performed to study the role of MARCH6 on thyroid cancer growth and metastasis. Immunoblotting and co-immunoprecipitation were used to dissect MARCH6 substrate in thyroid cancer. Findings: MARCH6 was upregulated in the majority of primary papillary thyroid cancers at both mRNA and protein level. Gain-of-function and loss-of-function studies demonstrated that MARCH6 suppressed apoptosis and promoted cell cycle progression, cell proliferation, migration and tumorigenesis. Mechanistically, MARCH6 interacted and downregulation of DHX9. Knockdown of DHX9 enhanced the proliferative and migrated viability of thyroid cancer cells. The inhibitory effect of MARCH6 knockdown on thyroid cancer cell growth and migration was also reversed by DHX9 silencing. In addition, MARCH6 also activated AKT/mTOR signaling pathway, which was depending on downregulation of DHX9. Interpretation: MARCH6 promotes thyroid cancer by destabilizing DHX9 and activation of AKT/mTOR. Funding: The study was funded by CAMS Innovation Fund for Medical Sciences (CIFMS) (Grant no.2016-I2m 1-001) and National Natural Science Foundation of China (Grant No. 81902728). Declaration of Interests: The authors confirm that they have no conflicts. Ethics Approval Statement: All experiments performed are endorsed by the Ethics of Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College and complied with the Declaration of Helsinki. All animal experiments were carried out with the approval of the Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College and Use Committee in accordance with the guidelines for the ethical treatment of animals.