The significance and prognostic value of multifocal papillary thyroid carcinoma in children and adolescents.

INTRODUCTION: The prognostic value of multifocality in paediatric papillary thyroid carcinoma (PTC) patients remains a subject of debate. This study aimed to explore the clinical significance and prognostic value of multifocality in children and adolescents with PTC. METHODS: This study retrospectively analysed the clinicopathological characteristics and postoperative follow-up data of 338 PTC patients aged ≤ 20 years from May 2012 to July 2022. The clinical and pathological characteristics of 205 patients with unifocal lesions and 133 patients with multifocal lesions were compared. A logistic regression model evaluated the relationship between multifocal lesions and disease recurrence/persistence in children and adolescents with PTC. Based on the median follow-up time of children with multifocal PTC, 114 patients with multifocal PTC older than 20 years were added, and the clinicopathological characteristics were compared between the 133. paediatric/adolescent patients and 114 adult patients with multifocal PTC. RESULTS: Among the paediatric and adolescent patients, over a median follow-up time of 49 months, 133 had multifocal disease and 205 had unifocal disease. Multifocal PTC patients exhibited stronger invasiveness in the form of extrathyroidal extension, tumour diameter, lymph node metastasis, and distant metastasis. Multifocality (OR 2.68; p = 0.017), lateral lymph node metastasis (OR 2.85; p = 0.036), and distant metastasis (OR 4.28; p = 0.010) were identified as independent predictive factors for the recurrence/persistence of disease. Comparing the paediatric/adolescent vs. adult multifocal patients, the former demonstrated greater tumour invasiveness. Lateral lymph node metastasis (OR 6.36; P = 0.012) and distant metastasis (OR 3.70; P = 0.027) were independent predictive factors for recurrence/persistence of disease in multifocal patients, while age was not (OR 0.95; P = 0.455). CONCLUSION: Tumour multifocality independently predicts persistent/recurrent disease in paediatric and adolescent PTC patients.

Multi-omics analysis-based macrophage differentiation-associated papillary thyroid cancer patient classifier.

BACKGROUND: The reclassification of Papillary Thyroid Carcinoma (PTC) is an area of research that warrants attention. The connection between thyroid cancer, inflammation, and immune responses necessitates considering the mechanisms of differential prognosis of thyroid tumors from an immunological perspective. Given the high adaptability of macrophages to environmental stimuli, focusing on the differentiation characteristics of macrophages might offer a novel approach to address the issues related to PTC subtyping. METHODS: Single-cell RNA sequencing data of medullary cells infiltrated by papillary thyroid carcinoma obtained from public databases was subjected to dimensionality reduction clustering analysis. The RunUMAP and FindAllMarkers functions were utilized to identify the gene expression matrix of different clusters. Cell differentiation trajectory analysis was conducted using the Monocle R package. A complex regulatory network for the classification of Immune status and Macrophage differentiation-associated Papillary Thyroid Cancer Classification (IMPTCC) was constructed through quantitative multi-omics analysis. Immunohistochemistry (IHC) staining was utilized for pathological histology validation. RESULTS: Through the integration of single-cell RNA and bulk sequencing data combined with multi-omics analysis, we identified crucial transcription factors, immune cells/immune functions, and signaling pathways. Based on this, regulatory networks for three IMPTCC clusters were established. CONCLUSION: Based on the co-expression network analysis results, we identified three subtypes of IMPTCC: Immune-Suppressive Macrophage differentiation-associated Papillary Thyroid Carcinoma Classification (ISMPTCC), Immune-Neutral Macrophage differentiation-associated Papillary Thyroid Carcinoma Classification (INMPTCC), and Immune-Activated Macrophage differentiation-associated Papillary Thyroid Carcinoma Classification (IAMPTCC). Each subtype exhibits distinct metabolic, immune, and regulatory characteristics corresponding to different states of macrophage differentiation.

Sciellin promotes the development and progression of thyroid cancer through the JAK2/STAT3 signaling pathway.

Thyroid cancer (TC) is one of the most common endocrine tumors worldwide. Sciellin (SCEL) is involved in various disease processes, including burn wound healing and neutrophil extracellular traps (NETs); it is highly expressed in TC. However, its biological impact on TC and related mechanisms remain unclear. This study aimed to investigate the effect of SCEL on the function of human TC cell lines B-CPAP and OCUT-2C (cancer cell lines with BRAF V600E mutations). Analyses of data sets and clinical samples revealed enhanced expression of SCEL in TC than in adjacent normal tissue. SCEL knockout suppresses proliferation and cell cycle progression in TC cells, and these results were reversed by the upregulated SCEL expression in TC. SCEL knockout inhibited tumor development in xenograft mouse models. Western blot (WB) demonstrated that the expression of p-JAK2 and p-STAT3 was reduced in SCEL-knockdown TC. These results suggest that SCEL plays a key role in TC progression through the JAK2-STAT3 pathway. Therefore, SCEL can be considered a potential diagnostic biomarker and therapeutic target for TC.

Ibuprofen inhibits anaplastic thyroid cells in vivo and in vitro by triggering NLRP3-ASC-GSDMD-dependent pyroptosis.

Pyroptosis is a novel type of proinflammatory programmed cell death that is associated with inflammation, immunity, and cancer. Anaplastic thyroid carcinoma (ATC) has a high fatality rate, and there is no effective or standard treatment. The disease progresses rapidly and these tumors can invade the trachea and esophagus, leading to breathing and swallowing difficulties. Hence, new treatment methods are greatly needed. Ibuprofen is a common drug that can exert antitumor effects in some cancers. In this study, we demonstrated in vitro and in vivo that ibuprofen can induce ATC pyroptosis. Hence, we treated C643 and OCUT-2C ATC cells with ibuprofen and found that several dying cells presented the characteristic morphological features of pyroptosis, such as bubble-like swelling and membrane rupture, accompanied by activation of ASC and NLRP3 and cleavage of GSDMD. Along with the increased release of LDH, ibuprofen treatment promoted apoptosis and inhibited viability, invasion, and migration. However, overexpression of GSDMD significantly inhibited ibuprofen-induced pyroptosis. In vivo, research has demonstrated that thyroid tumor growth in nude mice can be suppressed by ibuprofen-induced pyroptosis in a dose-dependent manner. In this research, we explored a new mechanism by which ibuprofen inhibits ATC growth and progression and highlighted its promise as a therapeutic agent for ATC.

LncRNA SOCS2-AS1 promotes the progression of papillary thyroid cancer by destabilizing p53 protein.

Long noncoding RNAs (lncRNAs) have been shown to contribute to tumorigenesis and cancer progression. However, neither the dysregulation nor the functions of anti-sense lncRNAs in papillary thyroid carcinoma (PTC) have been exhaustively studied. In this study, we accessed The Cancer Genome Atlas (TCGA) database and discovered that the natural antisense lncRNA SOCS2-AS1 is highly expressed in PTC and that patients with a higher level of SOCS2-AS1 had a poor prognosis. Furthermore, loss- and gain-function assays demonstrated that SOCS2-AS1 promotes PTC cell proliferation and growth both in vitro and in vivo. In addition, we demonstrated that SOCS2-AS1 regulates the rate of fatty acid oxidation (FAO) in PTC cells. Analysis of the mechanism revealed that SOCS2-AS1 binds to p53 and controls its stability in PTC cell lines. Overall, our findings showed that the natural antisense lncRNA SOCS2-AS1 stimulates the degradation of p53 and enhances PTC cell proliferation and the FAO rate.

A novel pharmacological mechanism of anti-cancer drugs that induce pyroptosis.

Pyroptosis is an inflammasome-induced lytic form of programmed cell death, and its main effect involves the release of inflammatory mediators when a cell dies, resulting in an inflammatory response in the body. The key to pyroptosis is the cleavage of GSDMD or other gasdermin families. Some drugs can cause cleavage GSDMD or other gasdermin members cause pyroptosis and suppress cancer growth and development. This review explores several drugs that may induce pyroptosis, thereby contributing to tumor treatment. Pyroptosis-inducing drugs, such as arsenic, platinum, and doxorubicin, were used originally in cancer treatment. Other pyroptosis-inducing drugs, such as metformin, dihydroartemisinin, and famotidine, were used to control blood glucose, treat malaria, and regulate blood lipid levels and are effective tumor treatments. By summarizing drug mechanisms, we provide a valuable basis for treating cancers by inducing pyroptosis. In future, the use of these drugs may contribute to new clinical treatments.

Nomogram model based on preoperative serum thyroglobulin and clinical characteristics of papillary thyroid carcinoma to predict cervical lymph node metastasis.

Objective: Preoperative evaluation of cervical lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC) has been one of the serious clinical challenges. The present study aims at understanding the relationship between preoperative serum thyroglobulin (PS-Tg) and LNM and intends to establish nomogram models to predict cervical LNM. Methods: The data of 1,324 PTC patients were retrospectively collected and randomly divided into training cohort (n = 993) and validation cohort (n = 331). Univariate and multivariate logistic regression analyses were performed to determine the risk factors of central lymph node metastasis (CLNM) and lateral lymph node metastasis (LLNM). The nomogram models were constructed and further evaluated by 1,000 resampling bootstrap analyses. The receiver operating characteristic curve (ROC curve), calibration curve, and decision curve analysis (DCA) of the nomogram models were carried out for the training, validation, and external validation cohorts. Results: Analyses revealed that age, male, maximum tumor size >1 cm, PS-Tg ≥31.650 ng/ml, extrathyroidal extension (ETE), and multifocality were the significant risk factors for CLNM in PTC patients. Similarly, such factors as maximum tumor size >1 cm, PS-Tg ≥30.175 ng/ml, CLNM positive, ETE, and multifocality were significantly related to LLNM. Two nomogram models predicting the risk of CLNM and LLNM were established with a favorable C-index of 0.801 and 0.911, respectively. Both nomogram models demonstrated good calibration and clinical benefits in the training and validation cohorts. Conclusion: PS-Tg level is an independent risk factor for both CLNM and LLNM. The nomogram based on PS-Tg and other clinical characteristics are effective for predicting cervical LNM in PTC patients.

AMPK-PPARγ-Cidec Axis Drives the Fasting-Induced Lipid Droplet Aggregation in the Liver of Obese Mice.

Intermittent fasting is one of the most common clinical treatments for the obesity, a main risk factor of the metabolic syndrome which can lead to a variety of diseases. Fasting-induced fat mobilization alters the metabolic state of lipid in the liver, predisposing to increase the hepatic lipid droplet aggregation and triglyceride levels. However, the underlying mechanisms regarding the lipid droplet aggregation in the liver after fasting remains elusive. Here, we report that a lipid droplet surface binding protein Cidec (cell death inducing DFFA like effector C) is activated by AMPK to regulate the hepatic lipid droplet fusion following fasting in obese mice. Specifically, we found that lipid droplets were significantly aggregated in the liver of high-fat-diet and ob/ob mice after 16 and 24 h of fasting, accompanied by the dramatically up-regulated expression of Cidec. Consistently, overexpression of Cidec in the AML12 cells resulted in the intracellular lipid droplet aggregation. Furthermore, we showed that fasting caused the up-regulated expression of AMPK, which in turn activated the transcription of Cidec through the transcription factor PPARγ. Altogether, our observations reveal that fasting-induced hepatic lipid droplet aggregation is mediated by the AMPK-activated expression of Cidec via PPARγ, extending our understanding about the molecular mechanism of the impact of fasting on the obesity and providing potential targets for the treatment of human obesity.

B cell subsets were associated with prognosis in elderly patients with community acquired pneumonia.

BACKGROUND: The role of B cell subsets remained to be elucidated in a variety of immune diseases, though which was used as an effective biomarker for anti-inflammatory or antiviral response. This study aimed to evaluate the early changes of B cell subtypes distribution in elderly patients with community acquired pneumonia (CAP), as well as the association between B cell subtypes and prognosis. METHODS: This prospective study included elderly patients with CAP, severe CAP (sCAP) and healthy elderly subjects between April 2016 and March 2018. Flow cytometry was used to detect CD3, CD20, HLA-DR, CD24, CD27, CD38, IgM, and IgD. CD20+ B cells were further divided into naïve B cells (Bn), IgM/D+ memory B cells (IgM+ Bm), switched B cells (SwB), and transitional B cells (Btr). RESULTS: A total of 22 healthy controls, 87 patients with CAP and 58 patients with sCAP were included in the study. Compared to CAP, sCAP was characterized by significantly lower absolute number of B cells, Bn and Btr, significantly lower Btr and Bn subset percentage, while percentage of IgM+ Bm was significantly higher. Heat map showed Bn and Btr on day 3 and day 7 was negatively correlated with activated partial prothrombin time (APTT), international normalized ratio (INR), sequential organ failure assessment score (SOFA) and Acute Physiology and Chronic Health Evaluation II (APACHE II). After 28-day follow-up, Btr percentage in survival group was significantly higher. Receiver operator characteristic (ROC) curve analysis found that Btr count showed sensitivity of 48.6% and specificity of 87.0% for predicting the 28-day survival, with an area under the ROC curves of 0.689 (p = 0.019). CONCLUSIONS: Severity and prognosis of CAP in elderly people is accompanied by changes in the B cell subsets. Btr subsets could play prognostic role for a short-term mortality of elderly CAP patients.

LncRNA CALML3-AS1 suppresses papillary thyroid cancer progression via sponging miR-20a-5p/RBM38 axis.

BACKGROUND: The incidence and mortality of thyroid cancer (TC) has been steadily rising in the past decades. It is imperative to have a better understanding of the molecular mechanisms underlying TC development and identify novel therapeutic targets. This study characterized the role of lncRNA CALML3-AS1 (CALML3-AS1) in the development of papillary thyroid cancer (PTC). METHOD: Related mRNAs expression were validated in the tumor and adjacent normal tissues from 52 PTC patients and PTC cell lines by qRT-PCR. Expression of RBM38 was detected by Western blot. We have also conducted CCK-8 and colony formation assays were used to detect the effect of CALML3-AS1 on cell proliferation, Transwell assay was utilized to evaluate cell migration and invasion, apoptosis detected by flow cytometry assay, RNA pull-down and luciferase assays were performed to validate gene predictions. RESULTS: The results indicated that the expression of both CALML3A-S1 and RBM38 were significantly downregulated in PTC tissues (p < 0.01), while the expression of miR-20a-5p was increased in PTC (p < 0.01). Functionally, CALML3-AS1 overexpression inhibited PTC cell proliferation in vitro and in vivo. Mechanistically, CALML 3-AS1 sponged miR-20a-5p, which in turn leads to the suppression of RBM38 expression and PTC progression. CONCLUSIONS: CALML3-AS1 functions as a ceRNA for miR-20a-5p in the regulation of the expression of RBM38 in PTC. Higher level of CALML3-AS1 serves as a good prognostic indicator of survival in PTC patients. Targeting CALML3-AS1/ miR-20a-5p/RBM38 axis may represent a novel therapeutic strategy in the treatment of PTC.

Upregulated SLC27A2/FATP2 in differentiated thyroid carcinoma promotes tumor proliferation and migration.

BACKGROUND: Differentiated thyroid carcinoma (DTC) accounts for the vast majority of thyroid cancer (TC) cases. The rapidly increasing incidence of TC requires the urgent identification of new diagnostic and therapeutic targets. Solute carrier family 27 member 2 (SLC27A2/FATP2) plays an essential role in lipid biosynthesis and fatty acid transport. Recent studies have confirmed its involvement in a variety of diseases, including cancer. METHODS: In this study, the expression of SLC27A2 was analyzed in cancer and paracancerous tissue samples from 98 thyroid cancer patients, and we performed ROC analysis to confirm the diagnostic value. CCK8, Transwell, and other methods were used to study its effect on DTC, and the mechanism of SLC27A2 was investigated by RNA sequencing and Western blot. RESULTS: The expression of SLC27A2 was upregulated in both DTC tissues and cell lines and was correlated with clinical progression. In vitro studies further confirmed that SLC27A2 knockdown attenuated the proliferation and invasion of DTC cells. Through RNA sequence analysis and gene set enrichment analysis, we found that the MAPK pathway is the main downstream signaling pathway for the regulation by SLC27A2. SLC27A2 affects cell proliferation and differentiation by inducing changes in the proto-oncogene C-FOS. CONCLUSIONS: Our results show that SLC27A2 plays an important role in tumor proliferation and migration, providing a new putative target for the diagnosis and treatment of TC.

Skin-inspired thermoelectric nanocoating for temperature sensing and fire safety.

Temperature sensing enables flammable materials to respond intelligently at high temperature, which is conducive to further improving their fire safety. However, it is still challenging to develop a smart nanocoating with sensitive temperature-sensing and efficient flame retardancy. Inspired by human skin, a thermoelectric flame retardant (TE-FR) nanocoating was fabricated by combining a dermis-mimicking thermoelectric (TE) layer and an epidermis-mimicking flame retardant (FR) layer. The TE-FR nanocoating exhibited accurate temperature sensing at 100-300 ℃ and repeatable fire-warning capability. When being burned, the fire-warning response time of the TE-FR nanocoating was only 2.0 s, and it retriggered the fire-warning device within 2.8 s when it was reburned. Meanwhile, the TE-FR nanocoating exhibited outstanding flame retardancy. The coated polypropylene self-extinguished in the horizontal and vertical burning tests. Besides, its peak heat release rate, total heat release, and peak smoke production rate were significantly reduced. This work proposed an ingenious strategy to fabricate smart nanocoating for temperature sensing and fire safety, which revealed an enticing prospect in the fields of fire protection, electronic skin, and temperature monitor.

Gut Microbiome Alterations in Patients With Thyroid Nodules.

Thyroid nodules are found in nearly half of the adult population. Accumulating evidence suggests that the gut microbiota plays an important role in thyroid metabolism, yet the association between gut microbiota capacity, thyroid nodules, and thyroid function has not been studied comprehensively. We performed a gut microbiome genome-wide association study in 196 patients with thyroid nodules and 283 controls by using whole-genome shotgun sequencing. We found that participants with high-grade thyroid nodules have decreased number of gut microbial species and gene families compared with those with lower grade nodules and controls. There are also significant alterations in the overall microbial composition in participants with high-grade thyroid nodules. The gut microbiome in participants with high-grade thyroid nodules is characterized by greater amino acid degradation and lower butyrate production. The relative abundances of multiple butyrate producing microbes are reduced in patients with high-grade thyroid nodules and the relative abundances of L-histidine metabolism pathways are associated with thyrotropin-releasing hormone. Our study describes the gut microbiome characteristics in thyroid nodules and a gut-thyroid link and highlight specific gut microbiota as a potential therapeutic target to regulate thyroid metabolism.

Increased Expression of hsa_circ_0002111 and Its Clinical Significance in Papillary Thyroid Cancer.

Circular RNA (circRNA) is a newly discovered non-coding RNA. Recent reports suggest that circRNAs are key regulators of tumorigenesis because of their special structure. In order to investigate the role of hsa_circ_0002111 in papillary thyroid cancer (PTC), we use quantitative real-time polymerase chain reaction (qRT-PCR) to determine the expression pattern of hsa_circ_0002111 in 82 paired PTC and adjacent non-cancerous thyroid tissues. Cell counting kit-8, colony formation, and transwell assays were conducted to assess the effect of hsa_circ_0002111 on PTC cell proliferation, migration, and invasion. We found that the expression of hsa_circ_0002111 was significantly up-regulated in PTC tissues compared with adjacent non-cancerous tissues (P < 0.0001). Expression of hsa_circ_0002111 was also associated with advanced TNM stage and lymph-node metastasis of patients with PTC. The area under the receiver operating characteristic curve was 0.833. Further, cell function assays showed that hsa_circ_0002111 inhibition significantly suppressed the proliferation and invasion abilities of PTC cells in vitro. In conclusions, the study findings show that the over-expression of hsa_circ_0002111 promotes PTC, and thus hsa_circ_0002111 may be a potential diagnostic biomarker and therapeutic target for PTC.

The Role of Exosomes in Thyroid Cancer and Their Potential Clinical Application.

The incidence of thyroid cancer (TC) is rapidly increasing worldwide. The diagnostic accuracy and dynamics of TC need to be improved, and traditional treatments are not effective enough for patients with poorly differentiated thyroid cancer. Exosomes are membrane vesicles secreted specifically by various cells and are involved in intercellular communication. Recent studies have shown that exosomes secreted by TC cells contribute to tumor progression, angiogenesis and metastasis. Exosomes in liquid biopsies can reflect the overall molecular information of tumors, and have natural advantages in diagnosing TC. Exosomes also play an important role in tumor therapy due to their special physicochemical properties. TC patients will benefit as more exosome patterns are discovered. In this review, we discuss the role of TC-derived exosomes in tumorigenesis and development, and describe the application of exosomes in the diagnosis and treatment of TC.

Inhibition of miR-25 attenuates doxorubicin-induced apoptosis, reactive oxygen species production and DNA damage by targeting PTEN.

Background: Doxorubicin (DOX) is one of the widely used anti-cancer drugs, whereas it can induce irreversible cardiac injury in a dose-dependent manner which limits its utility in clinic. Our study aimed to investigate the relationship between miR-25 and DOX-induced cardiac injury and its underlying mechanism. Methods: Mice and H9c2 cells were exposed to DOX. The overexpressed or knockdown of miR-25 in H9c2 cells was achieved by miR-25 mimic or inhibitor and the efficiency of transfection was identified by qRT-PCR or Western blotting. Cell viability, apoptotic cell rate, and levels of apoptosis-related proteins were determined by CCK-8, flow cytometry, and Western blotting, respectively. Furthermore, Western blotting and immunofluorescence staining (IF) were performed to assess the expression levels of reactive oxygen species and degree of DNA damage. Results: As a result, DOX significantly upregulated miR-25 expression in mice and H9c2 cells and reduced cell viability and increased cell apoptosis in vitro and in vivo. miR-25 overexpression expedited cell injury induced by DOX in H9c2 cells demonstrated by the increased cell apoptosis and reactive oxygen species (ROS) production, whereas miR-25 inhibition attenuated the cell injury. Furthermore, miR-25 negatively controlled the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN). Intervention the expression of PTEN using si-PTEN reversed the beneficial effects of miR-25 inhibition on DOX-injured H9c2 cells. Conclusion: In conclusion, this study demonstrated that miR-25 is involved in DOX-induced cell damage through the regulation of PTEN expression.

Circular RNA circEIF3I promotes papillary thyroid carcinoma progression through competitively binding to miR-149 and upregulating KIF2A expression.

Circular RNAs (circRNAs) have been shown to regulate the development and progression of various cancers. However, the expression and function of circRNAs in papillary thyroid cancer (PTC) remain largely unknown. This study is aimed to investigate the potential roles of circEIF3I in PTC and elucidate the functional mechanism. We found that the expression of circEIF3I was significantly upregulated in PTC tissues compared to adjacent normal tissues. CircEIF3I expression was positively associated with tumor size, TNM stage and metastasis. CircEIF3I knockdown remarkably suppressed the proliferation, migration and invasion of PTC cells. Mechanistically, circEIF3I promoted KIF2A expression through competitively interacting with miR-149. In conclusion, circEIF3I upregulation in PTC tissues facilitates KIF2A expression by inhibiting miR-149, leading to malignant progression of PTC. This study suggested circEIF3I/miR-149/KIF2A axis might be a potential therapeutic target.

Nomograms Predict Survival in Patients with Anaplastic Thyroid Carcinoma.

BACKGROUND Anaplastic thyroid carcinoma (ATC) is a very rare, highly lethal malignant cancer. Our aim in this study was to develop nomograms that predict survival in ATC patients. MATERIAL AND METHODS ATC incidence and mortality were assessed via joinpoint regression analysis of 567 ATC patients selected from the Surveillance, Epidemiology, and End Results 18 Registries Research database. Predictive models were established via univariate and multivariate Cox regression analysis of potential risk factors and used to produce nomograms. Performance of the nomograms in terms of discrimination ability and calibration was evaluated by determining the concordance index (C-index) and by generating calibration plots, respectively. RESULTS The incidence and mortality rates for ATC increased from 2000 to 2015 according to the collected data (p<0.05). Two nomograms were constructed based on 2 predictive models: nomogram 1 considered age, tumor size, and metastasis (all before surgery), and nomogram 2 considered age, tumor size, metastasis, surgery, and extrathyroidal extension (all after surgery). Both nomogram 1 (C-index, 0.6803; 95% confidence interval, 0.6517-0.7089) and nomogram 2 (C-index, 0.7064; 95% confidence interval, 0.6783-0.7345) had good discrimination ability. The validated C-index values were 0.6783 and 0.7029 for nomogram 1 and 2, respectively. The observed values were in agreement with the calibration curves. CONCLUSIONS Nomogram 1 can assist in preoperative prediction of survival time in ATC patients, whereas nomogram 2 can provide additional outcome-related information.

Upregulation of the long non-coding RNA FOXD2-AS1 is correlated with tumor progression and metastasis in papillary thyroid cancer.

BACKGROUND: Mounting evidence has shown that long non-coding RNAs (lncRNAs) play critical regulation roles in the progression of various cancers. However, the biological role and clinical value of lncRNA FOXD2-AS1 in papillary thyroid cancer (PTC) remain to be elucidated. METHODS: The expression of FOXD2-AS1 in PTC tissues and cell lines was evaluated by RT-qPCR and in situ hybridization. The association between FOXD2-AS1 expression levels and clinicopathologic features was analyzed through tissue microarray. The biological function of FOXD2-AS1 in PTC cells was determined both in vitro through CCK-8, EdU staining, colony formation and cell invasion assays and in vivo through a xenograft tumor model. Functional and pathway enrichment analysis were also conducted to analyze the molecular mechanism. RESULTS: FOXD2-AS1 was significantly upregulated in PTC tissues, and high FOXD2-AS1 expression was positively associated with malignant potential factors in PTC patients. In addition, high level of FOXD2-AS1 expression was an unfavorable independent prognostic biomarker for patients with PTC. Moreover, we found that knockdown of FOXD2-AS1 could effectively inhibit PTC cell proliferation and invasion in vitro and suppress tumor growth of PTC in vivo. Bioinformatics analysis indicated that activation of cell cycle and apoptosis pathways might be involved in the oncogenic function of FOXD2-AS1 in PTC. Moreover, we demonstrated that FOXD2-AS1 directly interacted with miR-185-5p as miRNA sponge and overexpression of FOXD2-AS1 partially reversed the suppressive effect of miR-185-5p in TPC cells. CONCLUSION: Our findings suggest FOXD2-AS1 functions as an oncogene and promotes the tumor progression and metastasis in PTC, which might serve as a promising prognostic biomarker and potential therapeutic target for PTC patients.