Suppression of MIR31HG affects the functional properties of thyroid cancer cells depending on the miR-761/MAPK1 axis.

BACKGROUND: Thyroid cancer is the most prevalent endocrine malignancy. Long non-coding RNA (lncRNA) MIR31HG is abnormally expressed in thyroid cancer tissues. However, the precise, critical role of MIR31HG in thyroid cancer development remains unclear. METHODS: MIR31HG, microRNA (miR)-761 and mitogen-activated protein kinase 1 (MAPK1) were quantified by quantitative real-time PCR (qRT-PCR) and immunoblotting. Cell viability, proliferation, apoptosis, invasion and migration abilities were evaluated by MTS, 5-Ethynyl-2'-Deoxyuridine (EdU), flow cytometry, transwell and wound-healing assays, respectively. Dual-luciferase reporter assays were used to validate the direct relationship between miR-761 and MIR31HG or MAPK1. RESULTS: MIR31HG was overexpressed in human thyroid cancer, and its overexpression predicted poor prognosis. Suppression of MIR31HG impeded cell proliferation, invasion and migration, as well as promoted cell apoptosis in vitro, and diminished the growth of xenograft tumors in vivo. Mechanistically, MIR31HG targeted and regulated miR-761. Moreover, miR-761 was identified as a molecular mediator of MIR30HG function in regulating thyroid cancer cell behaviors. MAPK1 was established as a direct and functional target of miR-761 and MAPK1 knockdown phenocopied miR-761 overexpression in impacting thyroid cancer cell behaviors. Furthermore, MIR31HG modulated MAPK1 expression by competitively binding to miR-761 via the shared binding sequence. CONCLUSION: Our findings demonstrate that MIR31HG targets miR-761 to regulate the functional behaviors of thyroid cancer cells by upregulating MAPK1, highlighting a strong rationale for developing MIR31HG as a novel therapeutic target against thyroid cancer.

Identifying Parathyroid Glands With Carbon Nanoparticle Suspension Does Not Help Protect Parathyroid Function in Thyroid Surgery: A Prospective, Randomized Control Clinical Study.

Objective We aim to evaluate the technique of identifying parathyroid glands with carbon nanoparticle suspension (CNPS) in thyroid surgeries from the perspectives of degrees of declining intact parathyroid hormone (iPTH), operation time, and time of postoperative stay. Methods A total of 156 patients who underwent thyroid surgeries in General Surgical Department of Xiangya Hospital between May 2012 and May 2015 were involved in the study. A total of 78 patients were injected with CNPS during the surgery (CNPS group); the other 78 patients received normal saline (control group). Cases were classified into 3 surgical approaches: conventional partial thyroidectomy, conventional total thyroidectomy, and endoscopic partial thyroidectomy. Degrees of declining iPTH were tested to determine the severity of parathyroid injury. Operation time and postoperative hospital stay time were recorded. A P value of less than .05 was considered statistically significant. Results For levels of declining iPTH, there was no statistically significant (ss) difference in conventional thyroid surgery. In endoscopic partial thyroidectomy, it was 23.37 ± 16.20 versus 11.94 ± 11.23 pg/mL (P = .02, ss). The operation time of conventional total thyroidectomy was 210.10 ± 83.75 versus 164.84 ± 69.22 minutes (P = .03, ss), while it was 193.04 ± 75.53 versus 127.67 ± 60.06 minutes (P = .007, ss) in endoscopic thyroidectomy. Conclusions CNPS is not beneficial for protecting the function of parathyroid gland in thyroid surgery from the perspective of declining iPTH. Applying CNPS in conventional total thyroidectomy and endoscopic partial thyroidectomy will also lead to significantly prolonged operation time.

[Clinical study on ambulatory surgery for thyroid].

OBJECTIVE: To evaluate the advantages and clinical value regarding the ambulatory surgery for thyroid.
 METHODS: A total of 66 patients (including 16 cases of differentiated thyroid cancer, 50 cases of benign thyroid tumors) from June 2014 to April 2015 in Center for Ambulatory Surgery of Xiangya Hospital were enrolled for this study and served as an exprimental group. All patients met pre-established ambulatory surgery criteria for thyroid. According to medical records, 133 patients with similar conditions to the experimental group were chosen as a control group. All of operations in two groups were completed by the same doctors. The time of operation, amount of bleeding during operation, drainage after the operation, operation method, resection range, histological features, surgical complications, average days of hospitalization, average hospitalization cost, the rate of re-admission and the satisfaction of patients were compared between the 2 groups. 
 RESULTS: Time of operation and amount of bleeding during operation were not significantly different between the 2 groups (P>0.05). In terms of drainage after operation and resection range, there were obvious differences between the 2 groups (P<0.05). The resection range and the amounts of drainage in the experimental group were less than those in the control group. More patients in the experimental group chose endoscopic thyroid surgery compared with those in the control group (P<0.05). The rate of surgical complications and re-admission was not different (P>0.05), but average days of hospitalization and average hospitalization cost were less in the experimental group (P<0.05). Patients were satisfied with ambulatory thyroid surgery (P<0.05).
 CONCLUSION: Under certain criteria, ambulatory surgery for thyroid is a new operation method, which is safe, high-efficient, convenient, economy and time-efficient. It can decrease average days of hospitalization and average hospitalization cost obviously, and provide a reasonable choice for certain patients. The selection of endoscopic thyroid surgery was not conflict with selection of ambulatory thyroid surgery.

Bioinformatics analyses of significant prognostic risk markers for thyroid papillary carcinoma.

This study was aimed to identify the prognostic risk markers for thyroid papillary carcinoma (TPC) by bioinformatics. The clinical data of TPC and their microRNAs (miRNAs) and genes expression profile data were downloaded from The Cancer Genome Atlas. Elastic net-Cox's proportional regression hazards model (EN-COX) was used to identify the prognostic associated factors. The receiver operating characteristic (ROC) curve and Kaplan-Meier (KM) curve were used to screen the significant prognostic risk miRNA and genes. Then, the target genes of the obtained miRNAs were predicted followed by function prediction. Finally, the significant risk genes were performed literature mining and function analysis. Total 1046 miRNAs and 20531 genes in 484 cases samples were identified after data preprocessing. From the EN-COX model, 30 prognostic risk factors were obtained. Based on the 30 risk factors, 3 miRNAs and 11 genes were identified from the ROC and KM curves. The target genes of miRNA-342 such as B-cell CLL/lymphoma 2 (BCL2) were mainly enriched in the biological process related to cellular metabolic process and Disease Ontology terms of lymphoma. The target genes of miRNA-93 were mainly enriched in the pathway of G1 phase. Among the 11 prognostic risk genes, v-maf avian musculoaponeurotic fibrosarcoma oncogene homologue F (MAFF), SRY (sex-determining region Y)-box 4 (SOX4), and retinoic acid receptor, alpha (RARA) encoded transcription factors. Besides, RARA was enriched in four pathways. These prognostic markers such as miRNA-93, miRNA-342, RARA, MAFF, SOX4, and BCL2 may be used as targets for TPC chemoprevention.

RNA interference targeting CD147 inhibits the proliferation, invasiveness, and metastatic activity of thyroid carcinoma cells by down-regulating glycolysis.

A high rate of glycolytic flux, even in the presence of oxygen, is a key metabolic hallmark of cancer cells. Lactate, the end product of glycolysis, decreases the extracellular pH and contributes to the proliferation, invasiveness and metastasis of tumor cells. CD147 play a crucial role in tumorigenicity, invasion and metastasis; and CD147 also interacts strongly and specifically with monocarboxylate transporter1 (MCT1) that mediates the transport of lactate. The objective of this study was to determine whether CD147 is involved, via its association with MCT1 to transport lactate, in glycolysis, contributing to the progression of thyroid carcinoma. The expression levels of CD147 in surgical specimens of normal thyroid, nodular goiter (NG), well-differentiated thyroid carcinoma (WDTC), and undifferentiated thyroid carcinoma (UDTC) were determined using immunohistochemical techniques. The effects of CD147 silencing on cell proliferation, invasiveness, metastasis, co-localization with MCT1, glycolysis rate and extracellular pH of thyroid cancer cells (WRO and FRO cell lines) were measured after CD147 was knocked-down using siRNA targeting CD147. Immunohistochemical analysis of thyroid carcinoma (TC) tissues revealed significant increases in signal for CD147 compared with normal tissue or NG, while UDTC expressed remarkably higher levels of CD147 compared with WDTC. Furthermore, silencing of CD147 in TC cells clearly abrogated the expression of MCT1 and its co-localization with CD147 and dramatically decreased both the glycolysis rate and extracellular pH. Thus, cell proliferation, invasiveness, and metastasis were all significantly decreased by siRNA. These results demonstrate in vitro that the expression of CD147 correlates with the degree of dedifferentiation of thyroid cancer, and show that CD147 interacts with MCT1 to regulate tumor cell glycolysis, resulting in the progression of thyroid carcinoma.