Long non-coding RNA FOXD2 Adjacent Opposite Strand RNA 1 (FOXD2-AS1) has been widely reported to be implicated in the progression and recurrence of several cancers. The clinical significance and functional role of FOXD2-AS1 in thyroid carcinoma remain unknown. FOXD2-AS1 expression was evaluated by analyzing thyroid cancer RNA sequencing dataset from The Cancer Genome Atlas (TCGA). In vitro and in vivo assays were performed to assess the biological roles of FOXD2-AS1 in thyroid cancer cells. Western blot, luciferase, immunoprecipitation (IP), and RNA immunoprecipitation (RIP) assays were used to identify the underlying miRNA and mRNA target mediating the biological roles of FOXD2-AS1 in thyroid cancer cells. FOXD2-AS1 was upregulated in thyroid carcinoma tissues and cells. High expression of FOXD2-AS1 significantly correlated with clinical stage, recurrence of thyroid carcinoma. Silencing FOXD2-AS1 inhibited cancer stem cell-like phenotypes and attenuates the anoikis resistance in vitro . Downregulating FOXD2-AS1 represses the tumorigenesis of thyroid carcinoma cells in vivo . FOXD2-AS1 acts as a competitive endogenous RNA (ceRNA) for miR-7-5p, up-regulating the expression of telomerase reverse transcriptase (TERT), which further promotes the cancer stem cells features and anoikis resistance in thyroid cancer cells. Our findings indicate that FOXD2-AS1 functions as an oncogenic regulator in the development of thyroid cancer, contributing to early recurrence of thyroid cancer.

miR-424-5p has been widely identified to function as an onco-miR in multiple human cancer types. However, the biological function of miR-424-5p in distant metastasis of thyroid cancer, as well as the underlying mechanism, remains not clarified yet. In the current study, miR-424-5p expression was elucidated in 10 paired fresh thyroid cancer tissues and the thyroid cancer dataset from The Cancer Genome Atlas (TCGA). Lung metastasis colonization models in vivo and functional assays in vitro were used to determine the role of miR-424-5p in thyroid cancer. Bioinformatics analysis, western blot, luciferase reporter, and immunofluorescence assays were applied to identify the potential targets and underlying mechanism involved in the functional role of miR-424-5p in lung metastasis of thyroid cancer. Here, we reported that miR-424-5p was upregulated in thyroid cancer, and overexpression of miR-424-5p significantly correlated with distant metastasis of thyroid cancer. Upregulating miR-424-5p promoted, whereas silencing miR-424-5p inhibited, anoikis resistance in vitro and lung metastasis in vivo. Mechanistic investigation further revealed that miR-424-5p promoted anoikis resistance and lung metastasis by inactivating Hippo signaling via simultaneously targeting WWC1, SAV1, and LAST2. Therefore, our results support the idea that miR-424-5p may serve as a potential therapeutic target in lung metastasis of thyroid cancer.

Purpose The institutional database of the Thyroid Surgery Division in China-Japan Union Hospital of Jilin University was queried to audit time trend patterns in thyroid cancer (TC) management between 2008 and 2017. Methods Retrospective longitudinal analysis. Clinicopathological features and treatment strategies were analyzed. Frequencies and multivariate tests were used to detect correlations. Results Clinical data were obtained from 15,000 TC patients (i.e., 71.3% of 21,044 operations). Papillary was the most common histological subtype (n = 14,916, 99%), and 76% were microcarcinomas. Stage I (95%) and low-risk patients (58%) were prevalent throughout the 10-year period. The trend for total thyroidectomy increased from 29.1% (2008-2012) to 67.9% (2013-2015), and then dropped to 48.6% (2016-2017). A total of 8827 (52%) patients received central lymph node dissection (CLND). The tendency for CLND increased from 15.7 to 86.4% during the 10-year period. While the trend of lateral lymph node dissection decreased from 71.3 to 13.3%. Radioactive iodine therapy was offered to 10% of patients (2008-2012), except for a low value (5.4%) in 2009, and then increased from 12.3% (2012) to 41.3% (2015), while decreased to 32.4% (2017). Conclusion The surgical management of TC patients has undergone continuous changes over the past 10 years. The evolution from aggressive treatment to a more conservative approach has been constant. Our results suggest that the current surgical management approach for TC is adequate and in support of the published guidelines. Our findings warrant further investigation to determine the clinical implications of decision making for TC.