A bibliometric analysis of follicular thyroid carcinoma: Current situation, hot spots, and global trends.

BACKGROUND: Follicular thyroid carcinoma (FTC), the second most prevalent thyroid cancer after papillary thyroid cancer (PTC), tends to metastasize distantly, leading to poorer outcomes. Despite substantial research, a holistic bibliometric analysis of FTC literature is lacking. This study aims to fill this gap by employing bibliometric methods to track FTC research evolution. METHODS: English FTC publications were systematically gathered from the Web of Science. Bibliometric analysis, using R, VOSviewer, CiteSpace, and Excel, synthesized data and explored global research trends and topics. RESULTS: From 2000 to 2023, 9086 authors from 1953 institutions across 75 countries contributed to 1776 papers in 491 academic journals on FTC. The last two decades have witnessed a steady increase in publications related to FTC, with the United States leading in terms of publication volume. The United States dominated both in publications and citations, with the National Cancer Institute and Sheue-Yann Cheng as leading contributors. The journal 'Thyroid' featured the most publications, while the 'Journal of Clinical Endocrinology and Metabolism' ranked highest in citation frequency. Research focused on gene expression analysis and preoperative diagnostics, with recent trends shifting toward prognosis management and machine learning due to advances in medical technology and increased health awareness. CONCLUSION: This comprehensive bibliometric analysis has mapped the landscape of FTC research, highlighting key contributors, institutions, and thematic trends. Current discourse predominantly revolves around genetic analysis, prognostic determinants, and preoperative diagnostics in FTC. This foundational work guides future FTC research, providing insights into its evolution.

Chiropractic rehabilitation in accelerated rehabilitation after total hip arthroplasty for Crowe type IV hip dysplasia.

To investigate the efficacy of chiropractic rehabilitation therapy in Crowe IV developmental dysplasia of the hip (DDH) patients after total hip arthroplasty. Seventy-two patients with Crowe IV type DDH hospitalized in the Department of Orthopedics I of Ya'an Hospital of Traditional Chinese Medicine from January 2021 to June 2023 were selected for the study, and they were divided into 36 cases in the chiropractic rehabilitation therapy group (the treatment group) and 36 cases in the traditional rehabilitation therapy group (the control group) according to the method of randomized grouping. All patients were evaluated at preoperative, 1, 3, and 6 months postoperatively for follow-up, and the muscle strength of the affected limb, the patient's walking gait, the shortened length of the affected limb, the visual analog scale score (VAS score), the Oswestry Dysfunction Index Score (ODI score), the Harris Hip Score, and the degree of pelvic tilt were recorded to evaluate the results of the study. A total of 4 subjects withdrew from the study, 2 in the treatment group, and 2 in the control group. The muscle strength of the affected limb, walking gait, shortened length of the affected limb, VAS score, ODI score, Harris score, and pelvic tilt in the treatment and control groups improved significantly compared with the preoperative period. Comparisons between the 2 groups revealed that at the final follow-up visit, the limp gait of the patients in the treatment group was significantly reduced, the shortened length of the affected limb was significantly reduced, the VAS score was significantly reduced, and the ODI score was significantly reduced, in the treatment group relative to that of the control group, Harris Hip Score was significantly improved, and the degree of pelvic tilt was significantly reduced, but the improvement in muscle strength of the affected limb was not statistically significant. In future clinical practice, we recommend that chiropractic rehabilitation be used as a routine adjunctive treatment after TKA in patients with Crowe IV DDH to optimize outcomes and improve patients' quality of life.

Incidental synchronous intrathyroidal parathyroid carcinomas and papillary thyroid microcarcinoma with compressive neck mass and primary hyperparathyroidism: case report and literature review.

BACKGROUND: Parathyroid carcinoma (PC) is a rare malignancy, often diagnosed incidentally through postoperative pathological examination. The occurrence of nodular goiter, intrathyroidal parathyroid carcinoma, contralateral parathyroid adenoma (PA), and papillary thyroid microcarcinoma (PTMC) is extremely uncommon, which prompted us to report our case experience. CASE PRESENTATION: We describe a 67-year-old male who presented with a cervical mass causing tracheal compression, which prompted him to seek medical advice. Based on preoperative auxiliary examination results from color Doppler ultrasound, SPECT parathyroid imaging, and blood tests, he was initially diagnosed with a suspected parathyroid adenoma and nodular goiter. Excision of the right lobe and isthmus of the thyroid, and left superior parathyroid gland was conducted, which were sent to intraoperative frozen pathological examination. During intraoperative observation, adhesion around the right thyroid lobe was discovered. Consequently, right central area lymph node dissection was performed due to suspicion of an aggressive malignant tumor. Histology and immunohistochemistry analysis revealed incidental intrathyroidal parathyroid carcinoma, contralateral parathyroid adenoma, classical papillary thyroid microcarcinoma, and nodular goiter. CONCLUSION: Parathyroid carcinoma should be highly suspected when extremely high levels of PTH and severe hypercalcemia are present, which cannot be simply explained by a preoperatively localized parathyroid adenoma, especially when suspicious malignant adhesion is found during intraoperative exploration. In cases where multifocal thyroid nodules are associated with increased uptake of 99Tc-sestamibi, the possibility of coexisting carcinomas should be considered, not only for thyroid malignancy but also for the potential presence of intrathyroidal parathyroid carcinoma.

Analysis of risk factors for lateral lymph node metastasis in T1 stage papillary thyroid carcinoma: a retrospective cohort study.

Background: The occurrence of cervical lymph node metastasis in T1 stage papillary thyroid carcinoma (PTC) is frequently observed. Notably, lateral lymph node metastasis (LLNM) emerges as a critical risk factor adversely affecting prognostic outcomes in PTC. The primary aim of this investigation was to delineate the risk factors associated with LLNM in the initial stages of PTC. Methods: This retrospective analysis encompassed 3,332 patients diagnosed with T1 stage PTC without evident LLNM at the time of diagnosis. These individuals underwent primary surgical intervention at West China Hospital, Sichuan University between June 2017 and February 2023. The cohort was divided into two groups: patients manifesting LLNM and those without metastasis at the time of surgery. Additionally, T1 stage PTC patients were subdivided into T1a and T1b categories. Factors influencing LLNM were scrutinized through both univariate and multivariate analyses. Results: The incidence of LLNM was observed in 6.2% of the cohort (206 out of 3,332 patients). Univariate analysis revealed significant correlations between LLNM and male gender (P<0.001), tumor localization in the upper lobe (P<0.001), maximal volume of the primary tumor (P<0.001), largest tumor diameter (P<0.001), multifocality (P<0.001), and bilaterality (P<0.001), with the exception of age (P=0.788) and duration of active surveillance (AS) (P=0.978). Multivariate logistic regression analysis identified male gender (P<0.001), upper lobe tumor location (P<0.001), maximal primary tumor volume (P<0.001), and multifocality (P<0.001) as independent predictors of LLNM. However, age categories (≤55, >55 years), maximum tumor diameter, bilaterality, and surveillance duration did not exhibit a significant impact. Comparative analyses between T1a and T1b subgroups showed congruent univariate results but revealed differences in multivariate outcomes. In the T1a subgroup, gender, tumor location, and multifocality (all P<0.05) were associated with elevated LLNM risk. Conversely, in the T1b subgroup, tumor location, dimensions, and multifocality (all P<0.05) were significant predictors of LLNM risk, whereas gender (P=0.097) exerted a marginal influence. Conclusions: The investigation highlights several key risk factors for LLNM in T1 stage PTC patients, including gender, upper lobe tumor location, larger tumor size, and multifocality. Conversely, prolonged AS and younger age did not significantly elevate LLNM risk, suggesting the viability of AS as a strategic option in selected cases.

Lacosamide extended-release capsules are bioequivalent to lacosamide immediate-release tablets: Pharmacokinetic observations and simulations.

OBJECTIVES: Assess the bioequivalence of lacosamide extended-release (XR) capsules and immediate-release (IR) tablets and answer real-world clinical questions regarding the use of lacosamide XR. METHODS: An open-label, randomized, two-treatment, two-sequence, oral comparative bioavailability study was conducted to assess the bioequivalence of two lacosamide formulations. Participants were randomized 1:1 to receive lacosamide XR capsules (400 mg once-daily) or IR tablets (200 mg twice-daily) in 1 of 2 sequences over 7-day periods. Primary outcome was the area under the lacosamide concentration-time curve over 24 h at steady-state (AUC0-τ,ss). Secondary outcomes were maximum (Cmax,ss) and minimum concentrations at steady-state (Cmin,ss). Bioequivalence was established when 90% confidence intervals (CIs) for geometric least square means ratios (GLSMs) were between 80% and 125%. Adverse events (AEs) and other safety outcomes were also assessed. Pharmacokinetic simulations, including adherent and partially adherent dosing scenarios with XR and IR formulations, modeled the clinical use of lacosamide XR. RESULTS: Thirty-five healthy adult males were enrolled in the bioequivalence study. After 7 days of study drug, mean AUC0-τ,ss, Cmax,ss, and Cmin,ss values were similar between XR and IR formulations; all 90% CIs for GLSMs were between 80% and 125%. AEs were mild and no serious AEs or other clinically significant safety findings were observed. Pharmacokinetic simulations suggested that partial adherence affected formulations similarly; and the best strategy for switching formulations was to take the morning lacosamide IR dose followed by the evening lacosamide XR dose, as this resulted in the most consistent lacosamide plasma concentrations. CONCLUSIONS: Once-daily lacosamide XR capsules were bioequivalent to twice-daily lacosamide IR tablets. Pharmacokinetic simulations indicated lacosamide XR and IR formulations were similarly affected by partial adherence, though once-daily dosing with lacosamide XR may offer clinical advantages, and formulations can be easily switched. These results support the use of lacosamide XR capsules as a once-daily alternative to lacosamide IR tablets.

A prospective study comparing the gasless endoscopic thyroidectomy trans-axillary approach to conventional open thyroidectomy: health and quality of life outcomes.

BACKGROUND: The relationship between different surgical treatments and quality of life remains uncertain for differentiated thyroid carcinoma (DTC). The aim of this study is to compare the gasless endoscopic thyroidectomy trans-axillary approach (ET) and traditional open thyroidectomy (OT) through a prospective cohort study focusing on the rate of the efficacy, and quality of life (QoL). METHODS: This prospective observational longitudinal cohort study enrolled 134 female patients diagnosed with DTC from December 01/2021 to December 31/2022. Multiple scales were applicated to evaluate the differences in quality of life, effectiveness, safety, etc. between the two groups during preoperative and postoperative follow-up periods, including the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, version 3.0 (QOL-C30), Symptom Checklist (SCL-90), Scar Cosmesis Assessment and Rating (SCAR-Q), voice impairment score (VIS), swallowing impairment score (SIS), and neck impairment score (NIS). RESULTS: Among them, 68 accepted ET and 66 patients underwent OT. To enhance comparability between the two groups, the patients enrolled in this study are female. Compared with the OT group, the ET group performed significantly better postoperative physical quality of life, including sound (p = 0.036), swallowing (p < 0.001), and neck function (p = 0.010). The ET group was also associated with significantly better cosmetic satisfaction (p < 0.001), and relatively faster recovery in psychological and emotional situation. CONCLUSIONS: Gasless endoscopic thyroidectomy through an axillary approach leads to good cosmetic and psychological effects, improves postoperative QoL, and could be recommended for rapid postoperative recovery and involvement in daily and social activities.

Effect of Radioactive Iodine Therapy on Cancer-Specific Survival of Papillary Thyroid Cancer Tall Cell Variant.

CONTEXT: Radioactive iodine (RAI) therapy is often used as an adjuvant treatment to reduce the risk of recurrence in patients with papillary thyroid cancer (PTC). However, the effect of RAI therapy on cancer-specific survival (CSS) in patients with tall cell variant (TCV) remains controversial. OBJECTIVE: This study aimed to investigate the impact of RAI therapy on CSS in patients with TCV-PTC by analyzing data from the Surveillance, Epidemiology, and End Results database. METHODS: We identified 1281 patients with TCV-PTC in the SEER database who underwent total thyroidectomy between 2004 and 2019. Of these, 866 (67.6%) patients received RAI therapy and 415 (32.4%) did not. Propensity score matching was conducted to balance the baseline characteristics between the 2 groups. Cox proportional hazards regression models were used to estimate the hazard ratio (HR) and 95% CI for the effect of RAI therapy on CSS. RESULTS: After propensity score matching, 373 pairs of patients were included in the analysis. The results showed no significant difference in CSS between the RAI therapy group and the non-RAI therapy group (HR 0.54, 95% CI 0.25-1.17, P = .120). Subgroup analyses indicated similar results. CONCLUSION: RAI therapy may not improve CSS in patients with TCV-PTC after total thyroidectomy. Future studies with larger sample sizes, longer follow-up periods, and better study designs are needed to confirm or refine our research findings.

Bibliometric insights in advances of endoscopic thyroidectomy: research status, hotspots, and global trends.

Background: Endoscopic thyroidectomy (ET) has witnessed significant advancements over the last three decades. Various surgical methods and approaches have been developed that minimize trauma, enhance aesthetics, and reduce psychological stress caused by scars. Papillary thyroid carcinoma is the main reason for thyroidectomy and ET represents an innovative technique for treating thyroid cancer. In this study, nearly three decades of scientific articles were analyzed and summarized to gain a better understanding by using bibliometric method. Methods: A total of 486 publications between 1996 and 2023 were retrieved from the Web of Science database through systematic searches. The objective of this study involved characterizing general information and investigating developmental trends and research frontiers. CiteSpace was employed to evaluate and visualize the results. Results: The query resulted 486 publications with a total citation frequency of 10,202. The top five countries in terms of the number of published articles were China, South Korea, the USA, Italy, and Japan. The top five countries in terms of literature centrality were Scotland, Israel, Brazil, the USA, and France. There were eight institutions with more than ten publications. The top ten institutions had a centrality score of 0.02 or above, indicating intensive research in this area and substantial collaboration among institutions. The most cited authors primarily originated from South Korea. Journals such as Surgical Endoscopy and Other Interventional Techniques, Surgical Laparoscopy Endoscopy & Percutaneous Techniques, Head and Neck Journal for the Sciences and Specialties of the Head and Neck, and Thyroid exerted considerable influence in this field. Keyword analysis results revealed that research predominantly focused on thyroid cancer and surgical approaches. Conclusions: This bibliometric study provides a comprehensive analysis of global productivity, collaboration, and research focus in the field of ET. The findings of this study serve as valuable guidance for future research in ET.

Gasless Endoscopic Thyroidectomy via the Trans-Axillary Approach.

For patients with early, low-risk papillary thyroid carcinoma, an increasing number are opting for endoscopic thyroid surgery due to its ability to achieve favorable therapeutic outcomes while maintaining excellent cosmetic results. Among the available endoscopic procedures, the Gasless Endoscopic Thyroidectomy Trans-axillary Approach (GETTA) has gained popularity among surgeons. This is attributed to its straightforward cavity construction, spacious operating area, precise visual field exposure, and manageable learning curve. However, few studies have provided detailed descriptions of the specific surgical steps involved in GETTA. Drawing from a synthesis of existing literature and our own clinical expertise, we present a comprehensive outline of the GETTA procedure. This process can be categorized into five distinct stages: positioning and incision planning; establishment of surgical cavities; identification and protection of the recurrent laryngeal nerve, inferior parathyroid gland, and central neck dissection; localization and preservation of the superior laryngeal nerve, superior parathyroid gland, and dissection of the thyroid's superior pole; transection of the thyroid isthmus followed by en bloc resection of the thyroid gland and central neck lymph nodes. The five-step approach of GETTA is easy to learn and can be adapted for resecting both benign and malignant thyroid and parathyroid diseases.

Therapeutic potential of Pseudomonas aeruginosa-mannose sensitive hemagglutinin (PA-MSHA) in cancer treatment.

Pseudomonas aeruginosa is a Gram-negative bacteria and it has been demonstrated that immunization with the outer membrane proteins of the microbe produces most of the relevant human antibodies. The peritrichous P. aeruginosa strain with MSHA fimbriae (PA-MSHA strain) has been found to be effective in the inhibition of growth and proliferation of different types of cancer cells. Furthermore, it has been revealed that PA-MSHA exhibits cytotoxicity because of the presence of MSHA and therefore it possesses anti-carcinogenic ability against different types of human cancer cell lines including, gastric, breast, hepatocarcinoma and nasopharyngeal cells. Studies have revealed that PA-MSHA exhibits therapeutic potential against cancer growth by induction of apoptosis, arrest of cell cycle, activating NF-κB/TLR5 pathway, etc. In China, PA-MSHA injections have been approved for the treatment of malignant tumor patients from very long back. The present review article demonstrates the therapeutic potential of PA-MSHA against various types of human cancers and explains the underlying mechanism.

Preoperative preparation for Graves' disease.

Thyroidectomy is always regarded as the crucial treatment for Graves' disease, especially in cases of poor efficacy or excessive side effects of antithyroid- drugs and 131I radioiodine therapy. To decrease the incidence of hemorrhage, thyroid storms and other severe complications during the perioperative period, surgeons explore different therapies to prepare for thyroidectomy. We performed a review of preoperative preparation with a focus on the Graves' disease population. Most of the previous schemes are effective, which contributes to the smooth operation of patients, but there is no unified standard for preoperative preparation. This review aims to summarize the preoperative preparation of Graves' disease and the latest developments. Prospective studies with longer follow up-up periods are required to select appropriate preoperative regimens based on personal thyroid statements and to identify target populations of benefit.

Endoscopic Gasless Trans-Axillary Parathyroidectomy for Patients with Primary Hyperparathyroidism: An Observational Retrospective Study.

Objective: The objective of this study is to evaluate the efficacy and safety of the gasless trans-axillary parathyroidectomy approach for the treatment of primary hyperparathyroidism in our medical center. Methods: A retrospective analysis was conducted on patients with single parathyroid adenoma who underwent parathyroidectomy using the gasless trans-axillary approach. Results: Between June 2020 and June 2022, 41 patients (37 women and 4 men) with primary hyperparathyroidism underwent endoscopic parathyroidectomy utilizing the gasless trans-axillary approach. Postoperative levels of parathyroid hormone and calcium showed a significant decline following the procedure. No permanent damage to the recurrent laryngeal nerve was observed. The mean adenoma size was 19.2 mm, with a volume of 2.66 mL. Successful identification and resolution of hyperparathyroidism were achieved for all patients. Conclusions: Endoscopic gasless trans-axillary parathyroidectomy is a safe and viable option for patients with primary hyperparathyroidism who wish to avoid cervical scarring. The surgical outcomes were favorable, and no major complications were encountered.

Developing an AI-assisted clinical decision support system to enhance in-patient holistic health care.

Holistic health care (HHC) is a synonym for complete patient care, and as such an efficient clinical decision support system (CDSS) for HHC is critical to support the judgement of physician's decision in response of patient's physical, emotional, social, economic, and spiritual needs. The field of artificial intelligence (AI) has evolved considerably in the past decades and many AI applications have been deployed in various contexts. Therefore, this study aims to propose an AI-assisted CDSS model that predicts patients in need of HHC and applies an improved recurrent neural network (RNN) model, long short-term memory (LSTM) for the prediction. The data sources include in-patient's comorbidity status and daily vital sign attributes such as blood pressure, heart rate, oxygen prescription, etc. A two-year dataset consisting of 121 thousand anonymized patient cases with 890 thousand physiological medical records was obtained from a medical center in Taiwan for system evaluation. Comparing with the rule-based expert system, the proposed AI-assisted CDSS improves sensitivity from 26.44% to 80.84% and specificity from 99.23% to 99.95%. The experimental results demonstrate that an AI-assisted CDSS could efficiently predict HHC patients.

Radioactive Iodine Therapy Does not Improve Cancer-specific Survival in Hürthle Cell Carcinoma of the Thyroid.

CONTEXT: It is unclear whether radioactive iodine (RAI) therapy could improve cancer-specific survival (CSS) in patients with Hürthle cell carcinoma (HCC) of the thyroid. OBJECTIVE: To investigate the effect of RAI on CSS in HCC patients. METHODS: HCC patients who underwent total thyroidectomy (TT) were identified from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2018. The Kaplan-Meier method and the Cox proportional hazards regression model were used to evaluate CSS. Propensity score-matched (PSM) analyses were performed to control the influence of potential confounders. RESULTS: A total of 2279 patients were identified. RAI treatment was not significantly associated with improved CSS in overall or PSM cohort. Subgroup analyses indicated similar results, even in patients with aggressive features such as age 55 years or older, tumor size greater than 40 mm, distant disease in SEER staging, extrathyroidal extension, and lymph node metastases (all P > .05). CONCLUSION: RAI has no statistically significant influence on the CSS in HCC patients. This information may aid in decision-making for RAI therapy in these patients.

High-dose vitamin D metabolite delivery inhibits breast cancer metastasis.

Besides its well-known benefits on human health, calcitriol, the hormonally active form of vitamin D3, has been being evaluated in clinical trials as an anticancer agent. However, currently available results are contradictory and not fundamentally deciphered. To the best of our knowledge, hypercalcemia caused by high-dose calcitriol administration and its low bioavailability limit its anticancer investigations and translations. Here, we show that the one-step self-assembly of calcitriol and amphiphilic cholesterol-based conjugates leads to the formation of a stable minimalist micellar nanosystem. When administered to mice, this nanosystem demonstrates high calcitriol doses in breast tumor cells, significant tumor growth inhibition and antimetastasis capability, as well as good biocompatibility. We further reveal that the underlying molecular antimetastatic mechanisms involve downregulation of proteins facilitating metastasis and upregulation of paxillin, the key protein of focal adhesion, in primary tumors.

Impact of Extent of Surgery on Long-Term Prognosis of Follicular Thyroid Carcinoma Without Extrathyroidal Extension and Distant Metastasis.

AIM: To analyze the effect of total thyroidectomy (TT) and thyroid lobectomy (LT) on the long-term prognosis of follicular thyroid carcinoma (FTC) without extrathyroidal extension and distant metastasis and to clarify whether the tumor size (≤ 40 mm vs. > 40 mm) has an important impact on the extent of surgery. METHODS: Data on FTC patients without extrathyroidal extension and distant metastasis treated with either TT or LT between 1998 and 2016 were extracted from the Surveillance, Epidemiology, and End Results Database. Propensity score matching was performed to minimize impact of selection bias and potential confounding. Kaplan-Meier curves and Cox regression analysis were conducted to assess the impact of the extent of surgery on disease-specific survival (DSS). RESULTS: A total of 8435 patients were identified. The DSS after LT were 100%, 98.3%, and 97.6% at 5, 10, and 15 years, respectively, compared with those seen after TT of 99.3%, 97.9%, and 96.6%. The difference between the two groups is not statistically significant (p = 0.083). Similar results were observed in cohorts after adjusting for baseline covariates. There was also similar prognosis between LT and TT in patients with tumors size ≤ 40 mm or > 40 mm. CONCLUSIONS: For patients with FTC of any size without extrathyroidal extension and distant metastases at diagnosis, TT and LT confer equivalent DSS. Completion thyroidectomy after LT may be not necessary unless patients relapse; however, recurrence rates and development of metastases are not evaluated in this study.

Genetic and clinical profiles of 160 papillary thyroid cancers with lateral neck lymph node metastasis.

Background: Lymph node metastasis is widespread in papillary thyroid cancer (PTC). Patients are more vulnerable than those with central lymph node metastasis if they have lateral neck lymph node metastasis (LLNM). There are few researches focus on the correlation between clinical characteristics and genetic profile of PTC with LLNM. In this study, we aimed to analyze the clinical and genetic features of PTC with LLNM. Methods: A total of 160 primary tumor samples derived from PTC patients with LLNM were involved. Targeted next-generation sequencing was carried out on all samples with 57 known thyroid-cancer-related genes. The associations between genomic alternations and clinical characteristics of PTC with LLNM were statistically evaluated. Results: The median age of patients was 37 years, ranging from 5 to 77 years and the female/male ratio was 1.86. The most frequently altered genes in our series were BRAF mutation (68%), followed by RET fusion (17%), TERT promoter mutation (5%) and PIK3CA mutation (2%). To be noted, all PTC patients with LLNM of TERT promoter mutations appeared along with BRAF mutations (8/8) and half of them experienced a relapse. Intriguingly, we found more metastatic lymph nodes in patients with RET fusion, but there was no statistically significant difference in metastatic lymph node ratio than those with BRAF mutation or without mutation. A high rate of gene fusion (70%) was found in the pediatric population, with aggressive late-onset disease. Conclusions: PTC patients with LLNM is characterized by a high rate of BRAF mutation. Due to the observed clinicopathological differences in those patients among different alterations, further prospective studies are needed to verify our results and to evaluate the most suitable treatment strategies.

LncRNA LINC00152 promotes oral squamous cell carcinoma growth via enhancing Upstream Transcription Factor 1 mediated Mitochondrial Ribosomal Protein L52 transcription.

BACKGROUND: LINC00152 (long intergenic non-protein coding RNA 152) was identified as an oncogenic lncRNA in multiple cancers. In the current study, we aimed to explore the transcriptional profile of LINC00152 in oral squamous cell carcinoma (OSCC) and its regulations at the transcriptional level. METHODS: Bioinformatic analysis was performed by extracting the OSCC subset from The Cancer Genome Atlas (TCGA)-Head and Neck Squamous Cell Carcinoma (HNSC). LINC00152 subcellular localization and its interacting transcriptional factors (TFs) were explored. Dual-luciferase assay and ChIP-qPCR were applied to study transcriptional regulation. In vitro and in vivo tumor cell growth models were used for functional assays. RESULTS: NR_024206.2 was the dominant isoform that accounts for 80% of all transcripts of LINC00152. LINC00152 upregulation was associated with unfavorable survival of patients with OSCC. LINC00152 knockdown significantly impaired OSCC cell growth in vitro and in vivo. RNA FISH assay confirmed nuclear and cytoplasmic distribution of LINC00152. It physically interacted with Upstream Transcription Factor 1 (USF1), a common transcription factor in mammalian cells. USF1 could bind to the promoter region of MRPL52 (Mitochondrial Ribosomal Protein L52) and activate its transcription. LINC00152 could enhance the binding, thereby indirectly elevating MRPL52 expression. USF1 or MRPL52 knockdown slowed the proliferation of OSCC cells and partly canceled LINC00152-mediated growth-promoting effects. CONCLUSION: This study revealed a novel LINC00152-USF1/MRPL52 axis promoting OSCC tumor growth.

circPVT1 regulates medullary thyroid cancer growth and metastasis by targeting miR-455-5p to activate CXCL12/CXCR4 signaling.

BACKGROUND: Medullary thyroid cancer (MTC) represents 13.4 % of all thyroid cancers-related deaths. The treatments for MTC are very limited especially for patients with distal metastasis. Therefore, it is critical to understand the mechanisms of MTC to pursue novel therapeutic avenues. Here, we studied the function of circPVT1/miR-455-5p in MTC. METHODS: Human MTC tissues and cell lines were used. qRT-PCR and Western blotting were employed to measure expression levels of miR-455-5p, circPVT1, CXCL12, and epithelial mesenchymal transformation (EMT)-related proteins. Colony formation assay, flow cytometry, transwell assay, and scratch wound healing assay were used to assess the abilities of cell proliferation, apoptosis, migration and invasion, respectively. Dual luciferase assay and RNA immunoprecipitation were employed to validate interactions of circPVT1/miR-455-5p and miR-455-5p/CXCL12. Nude mouse xenograft model was used to evaluate the effects of shcircPVT1 and miR-455-5p mimics on tumor growth and metastasis in vivo. RESULTS: miR-455-5p was reduced in MTC tissues and cells while circPVT1 was elevated. Their levels were correlated with prognosis of MTC. Overexpression of miR-455-5p or sh-circPVT1 suppressed EMT and MTC cell proliferation, migration and invasion. miR-455-5p targeted CXCL12 while circPVT1 sponged miR-455-5p. Knockdown of CXCL12 or CXCL12/CXCR4 signaling inhibitor reversed the effects of circPVT1 overexpression or miR-455-5p inhibitor on EMT and MTC cell proliferation, migration and invasion. Knockdown of circPVT1 or miR-455-5p overexpression repressed MTC tumor growth and lung metastasis in vivo. CONCLUSIONS: miR-455-5p suppresses MTC growth and metastasis by targeting CXCL12/CXCR4 signaling pathway while circPVT1 promotes MTC by sponging miR-455-5p. Our study sheds light on the mechanisms of MTC growth and metastasis.