RNF115 aggravates tumor progression through regulation of CDK10 degradation in thyroid carcinoma.

BACKGROUND: RING Finger Protein 115 (RNF115), a notable E3 ligase, is known to modulate tumorigenesis and metastasis. In our investigation, we endeavor to unravel the putative function and inherent mechanism through which RNF115 influences the evolution of thyroid carcinoma (THCA). METHODS: We analyzed RNF115 expression in THCA using the Cancer Genome Atlas (TCGA) database. The influence of RNF115 on the progression of THCA was evaluated using both in vitro and in vivo experimental approaches. The protein regulated by RNF115 was identified through bioinformatics analysis, and its biological significance was further explored. RESULTS: In both THCA tissues and cells, RNF115 showed elevated expression levels. Enhanced expression of RNF115 fostered cell proliferation, tumor growth, and the exacerbation of epithelial-mesenchymal transition (EMT) in THCA, while also promoting tumor lung metastasis. Bioinformatics analysis identified cyclin-dependent kinase 10 (CDK10) as a downstream target of RNF115, which was found to be ubiquitinated and degraded by RNF115 in THCA cells. Functionally, overexpression of CDK10 was found to counteract the promotion of malignant phenotype in THCA induced by RNF115. From a mechanistic perspective, RNF115 activated the Raf-1 pathway and enhanced cancer cell cycle progression by degrading CDK10 in THCA cells. CONCLUSION: RNF115 triggers cell proliferation, EMT, and tumor metastasis by ubiquitinating and degrading CDK10. The regulation of the Raf-1 pathway and cell cycle progression in THCA may be profoundly influenced by this process.

Amyloid-ß Oligomer-Induced Electrophysiological Mechanisms and Electrical Impedance Changes in Neurons.

Amyloid plays a critical role in the pathogenesis of Alzheimer's disease (AD) and can aggregate to form oligomers and fibrils in the brain. There is increasing evidence that highly toxic amyloid-ß oligomers (AßOs) lead to tau protein aggregation, hyperphosphorylation, neuroinflammation, neuronal loss, synaptic loss, and dysfunction. Although the effects of AßOs on neurons have been investigated using conventional biochemical experiments, there are no established criteria for electrical evaluation. To this end, we explored electrophysiological changes in mouse hippocampal neurons (HT22) following exposure to AßOs and/or naringenin (Nar, a flavonoid compound) using electrical impedance spectroscopy (EIS). AßO-induced HT22 showed a decreased impedance amplitude and increased phase angle, and the addition of Nar reversed these changes. The characteristic frequency was markedly increased with AßO exposure, which was also reversed by Nar. The AßOs decreased intranuclear and cytoplasmic resistance and increased nucleus resistance and extracellular capacitance. Overall, the innovative construction of the eight-element CPE-equivalent circuit model further reflects that the pseudo-capacitance of the cell membrane and cell nucleus was increased in the AßO-induced group. This study conclusively revealed that AßOs induce cytotoxic effects by disrupting the resistance characteristics of unit membranes. The results further support that EIS is an effective technique for evaluating AßO-induced neuronal damage and microscopic electrical distinctions in the sub-microscopic structure of reactive cells.

Genetic effects of inflammatory cytokines on coronary artery disease and myocardial infarction and the mediating roles of lipid traits.

BACKGROUND: Chronic inflammation has been connected by epidemiological evidence to coronary artery disease (CAD) along with myocardial infarction (MI). Nevertheless, it is still unclear whether reverse causality or confounders account for these connections. Our objectives are to examine the causality between inflammatory cytokines and CAD/MI as well as the potential mediating influence of lipid characteristics. METHODS: We acquired instrumental variables through genome-wide association studies meta-analyses of 41 inflammatory cytokines (8293 individuals). Genetic associations with CAD (122 733 cases and 424 528 controls), MI (~61 505 cases and 577 716 controls) and five candidate lipid mediators were obtained from the corresponding genome-wide association studies. A two-step, two-sample Mendelian randomization analysis was applied, followed with comprehensive sensitivity analyses. RESULTS: Genetically determined growth regulated oncogene-α was causally linked to a decreased incidence of CAD [odds ratio (OR), 0.97; 95% confidence interval (CI), 0.95-0.99; P = .007] and MI (OR, 0.95; 95% CI, 0.92-0.98; P = .002). There is suggestive evidence indicating a causal impact of macrophage inflammatory protein-1ß upon CAD (OR, 1.04; 95% CI, 1.01-1.07; P = .010) and MI (OR, 1.07; 95% CI, 1.02-1.11; P = .002). Furthermore, we discovered suggestive causal connections between tumor necrosis factor-related apoptosis-inducing ligand and CAD (OR, 0.97; 95% CI, 0.95-1.00; P = .020). Two-step Mendelian randomization analysis revealed that triglycerides partially mediate the effect of growth regulated oncogene-α on CAD (proportion-mediated: 13.28%) and MI (8.05%). CONCLUSIONS: We provided novel genetic evidence supporting the causality of inflammatory cytokines on CAD/MI and elucidate the mediating effect of triglycerides in the causal pathways linking inflammatory cytokines and CAD/MI.

Structural stability and electronic and mechanical properties of nitrogen- and boron-doped fluorinated diamane.

In this work, the structural, electronic and mechanical properties of fluorinated diamane (F-diamane) with N and B dopants are systemically investigated using first-principles calculation. The N atom tends to stay in the external substituted site without F saturation, while the B-doped structure of the substituted external site with F saturation is the most stable. Ab initio molecular dynamics simulations confirm the thermal stability. The band structures of stable doped structures are similar to that of pristine F-diamane, due to the slight contribution of the dopant to the band edges. In addition, after the introduction of the B dopant, the formation energy reduces, and the transition barrier of graphene bilayers into diamane is smaller, indicating the feasibility of graphene bilayer fluoridation. Furthermore, we find that these doped structures have mechanical stability with isotropic elastic constants, Young's modulus, shear modulus and Poisson's ratio. Our work would promote the synthesis and development of two-dimensional diamane.

Proliferation inhibition and apoptosis of liver cancer cells treated by blue light irradiation.

Blue light (BL) irradiation has been a potentially efficient treatment for many kinds of tumors. In this study, a BL irradiation (centered at 453 nm in wavelength) was proposed to treat the common human liver cancer cell lines of SMMC-7721 and HepG2, examined by means of flow cytometry, western blot, fluorescence microscope assay. In comparison to control groups, the apoptosis and proliferation inhibition of both BL-treated cells are expressively enhanced by mitochondrial apoptosis. The mechanism of apoptosis is related to the more production of reactive oxygen species (ROS) induced by BL and the corresponding changes in the expression of apoptosis-related Bcl-2, Bax and Bad proteins. In addition, the migration rate of the cancer cells could be reduced after BL irradiation. These results demonstrate that introducing BL irradiation is helpful to establish an effective and low toxicity strategy for the clinical treatment of liver tumors.

The Feasibility Study of Intraoperative RLN Monitoring Using Cricothyroid Membrane-Inserted Needle Electrodes During Thyroid Surgery.

OBJECTIVE: This study evaluated the feasibility, stability, safety, and economy of cricothyroid membrane (CM)-inserted needle electrodes for recurrent laryngeal nerve monitoring. STUDY DESIGN: Parallel and controlled study. SETTING: Clinical research center for thyroid diseases of Shaanxi province. METHODS: A total of 64 patients in the needle electrodes group (104 recurrent laryngeal nerves [RLNs]) and 44 patients in the endotracheal tube (ETT)-based electrodes group (80 RLNs) underwent monitored thyroidectomy. The evoked electromyography (EMG) signals detected by the 2 electrodes were recorded and analyzed. The changes in EMG during Berry's ligament traction and tracheal displacement were compared. All patients underwent preoperative and postoperative laryngoscopy within 1 week. RESULTS: Both electrodes successfully recorded typical evoked laryngeal EMG waveforms from RLNs. The needle electrodes recorded relatively higher amplitudes and similar latencies compared to ETT-based electrodes. The evoked EMG signals attributed to needle electrodes could accurately predict the function of RLNs with 100% sensitivity and specificity. The reduction in the recorded amplitudes attributed to needle electrodes was higher than that observed with ETT-based electrodes during Berry's ligament traction or trachea displacement, whereas a similar increase in the latencies was recorded in the 2 groups. Particularly, Berry's ligament traction was more likely to lead to EMG amplitude reduction and latency prolongation. The needle electrodes group recorded 2 cases of minor bleeding on the CM. The needle electrodes were more cost-effective than ETT-based electrodes. CONCLUSION: The CM-inserted needle electrodes are feasible, stable, safe, and economical for RLN monitoring, and they provide an alternative novel intraoperative neural monitoring format for thyroid surgeons.

Regulation of Hippo/YAP signaling pathway ameliorates cochlear hair cell injury by regulating ferroptosis.

Cisplatin, which is effective for the treatment of solid tumors, also can induce cochlear hair cell damage. Therefore, this study was intended to explore how Hippo/YAP signaling pathway affects the cochlear hair cell injury by regulating ferroptosis. After cisplatin induction, or LAT1-IN-1 (YAP activator) and verteporfin (YAP inhibitor) treatment or transfection, the viability of HEI-OC1 cells was detected by cell counting kit-8 (CCK-8) assay. The iron level and the levels of oxidative stress markers (ROS, MDA and 4-HNE) were analyzed by iron assay kit, reactive oxygen species (ROS), malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) assay kits, respectively. The expression of ferritin light chain (FTL) in HEI-OC1 cells was detected by immunofluorescence and protein expressions of yes associated protein (YAP,) phosphorylated YAP (p-YAP), transferrin receptor (TFRC), glutathione peroxidase 4 (GPX4), acyl-CoA synthetase long-chain family member 4 (ACSL4) and solute carrier family 7 member 11 (SLC7A11) in HEI-OC1 cells were detected by western blot. The transcription of FTL and TFRC by YAP1 was verified by dual-luciferase reporter assay. The transfection efficiency of small interfering RNA (si-RNA) specific to FTL (siRNA-FTL) and TFRC (siRNA-TFRC) was confirmed by reverse transcription­quantitative polymerase chain reaction (RT­qPCR). As a result, cisplatin inhibited the viability of HEI-OC1 cells by increasing free Fe2+ level and decreasing FTL level. LAT1-IN-1 promoted the viability of cisplatin-induced HEI-OC1 cells by suppressing oxidative stress level, free Fe2+ level, ferroptosis and increasing FTL level, while the effect of verteporfin was the opposite. YAP1 transcriptionally regulated the expression of FTL and TFRC. Inhibition of FTL suppressed the viability of cisplatin-induced HEI-OC1 cells by increasing oxidative stress level, free Fe2+ level, ferroptosis and decreasing FTL level, while the effect of TFRC inhibition was the opposite. In conclusion, YAP1 ameliorated cochlear hair cell injury by upregulating FTL and TFRC to suppress ferroptosis.

[Progress in active surveillance for adult low-risk papillary thyroid microcarcinoma].

The incidence of papillary thyroid microcarcinoma （PTMC） increases rapidly. However, epidemiological and autopsy studies show that the prevalence of low-risk papillary thyroid microcarcinoma （LR-PTMC） is very high, but the mortality is very low. There is over-diagnosis and over-treatment for LR-PTMC. Active surveillance （AS） was adopted for LR-PTMCs instead of immediate surgery, and more than 70% of the lesions remained stable or shrank in clinical observation. Therefore, AS is recommended for LR-PTMCs in clinical guidelines of several academic organizations around the world. However, PTMC is not equal to low-risk cancer. The implementation of AS strategy requires a strict grasp of indications and full consideration of population characteristics to ensure the maximum benefit of patients. This paper summarizes the present clinical progress of active surveillance for adult LR-PTMC.

SKP2 Contributes to AKT Activation by Ubiquitination Degradation of PHLPP1, Impedes Autophagy, and Facilitates the Survival of Thyroid Carcinoma.

Papillary thyroid carcinoma (PTC) is the most common subtype of thyroid carcinoma. Despite a good prognosis, approximately a quarter of PTC patients are likely to relapse. Previous reports suggest an association between S-phase kinase-associated protein 2 (SKP2) and the prognosis of thyroid cancer. SKP1 is related to apoptosis of PTC cells; however, its role in PTC remains largely elusive. This study aimed to understand the expression and molecular mechanism of SKP2 in PTC. SKP2 expression was upregulated in PTC tissues and closely associated with clinical diagnosis. In vitro and in vivo knockdown of SKP2 expression in PTC cells suppressed cell growth and proliferation and induced apoptosis. SKP2 depletion promoted cell autophagy under glucose deprivation. SKP2 interacted with PH domain leucine-rich repeat protein phosphatase-1 (PHLPP1), triggering its degradation by ubiquitination. Furthermore, SKP2 activates the AKT-related pathways via PHLPP1, which leads to the cytoplasmic translocation of SKP2, indicating a reciprocal regulation between SKP2 and AKT. In conclusion, the upregulation of SKP2 leads to PTC proliferation and survival, and the regulatory network among SKP2, PHLPP1, and AKT provides novel insight into the molecular basis of SKP2 in tumor progression.

Regulation of PPARγ/CPT-1 expression ameliorates cochlear hair cell injury by regulating cellular lipid metabolism and oxidative stress.

This study aimed to investigate the protective effects of PPARγ/CPT-1 regulation on cisplatin-induced cochlear hair cell injury. The viability, apoptosis and mitochondrial membrane potential of cisplatin-induced HEI-OC1 cells were determined by CCK-8 assay, TUNEL and JC-1 staining, respectively. The oxidative stress and lipid metabolism were detected by the assay kits of MDA, ROS, SOD, CAT, TG and FFA. The transfection efficiency of overexpression (OV)-PPARG and OV-CPT1A was examined by RT-qPCR and the expressions of apoptosis- and lipid metabolism-related proteins were detected by western blot. As a result, cisplatin with varying concentrations (5, 10, 30 µM) suppressed the viability, promoted the apoptosis and hindered the mitochondrial function of HEI-OC1 cells, accompanied with up-regulated expressions of Bax and cleaved caspase-3 and down-regulated expression of Bcl-2. The oxidative stress was aggravated and lipid metabolism was inhibited by cisplatin (5, 10, 30 µM) induction, evidenced by the increased levels of MDA, ROS, TG, FFA and the decreased levels of SOD and CAT. Overexpression of PPARG or CPT1A could improve the viability, mitochondrial function, lipid metabolism and suppress the oxidative stress and apoptosis of cisplatin-induced HEI-OC1 cells. In conclusion, up-regulation of PPARG or CPT1A ameliorated cochlear hair cell injury by improving cellular lipid metabolism and inhibiting oxidative stress.

IGFL2-AS1 facilitates tongue squamous cell carcinoma progression via Wnt/ß-catenin signaling pathway.

OBJECTIVES: Tongue squamous cell carcinoma (TSCC) is the most common malignancy in oral cancer. Long noncoding RNAs (lncRNAs) are important regulators in cancer biology. In our present study, we investigated a novel lncRNA IGF-like family member 2 antisense RNA 1 (IGFL2-AS1) in TSCC. METHODS: RT-qPCR analyzed IGFL2-AS1 expression in TSCC cells. Functional assays assessed the impact of IGFL2-AS1 on TSCC cell proliferation, migration, and invasion. Western blot analyzed the protein levels of EMT-related markers. Mechanism assays analyzed the regulatory mechanism of IGFL2-AS1 in TSCC cells. In-vivo experiments were conducted to prove the role of IGFL2-AS1 in TSCC progression. RESULTS: IGFL2-AS1 was significantly up-regulated in TSCC cells and tissues, and IGFL2-AS1 knockdown inhibited cell proliferation, migration, invasion and EMT in TSCC. Moreover, IGFL2-AS1 functioned as a competing endogenous RNA (ceRNA) to sponge miR-1224-5p and thereby modulated SATB homeobox 1 (SATB1) expression. Additionally, SATB1 activated the Wnt/ß-catenin signaling pathway in TSCC cells and IGFL2-AS1 regulated the Wnt/ß-catenin signaling pathway and TSCC progression via elevating SATB1 expression. CONCLUSIONS: The data revealed that IGFL2-AS1 played a cancer promoting role in TSCC and may aid in exploring a brand new biomarker that might contribute to TSCC treatment.

Circular RNA hsa_circ_0003892 promotes the development of papillary thyroid carcinoma by regulating the miR-326/LASP1 axis.

BACKGROUND: Thyroid cancer is the most common malignancy of the endocrine system. Circular RNA (circRNA) is recognized as a key regulator of tumorigenesis in papillary thyroid carcinoma (PTC). Here this work focused on the mechanism of circRNA_0003892 (circ_0003892) in PTC progression. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to examine circ_0003892, microRNA-326 (miR-326) and LIM and SH3 protein 1 (LASP1) mRNA expression levels in PTC tissues and cell lines. Besides, cell counting kit-8 (CCK-8), EdU and transwell assays were conducted to detect the proliferative, migrative and invasive abilities of PTC cells, respectively. B The targeting relationships between miR-326 and circ_0003892 or LASP1 3'-UTR were verified by dual-luciferase reporter gene assay and RNA immunoprecipitation (RIP) assay. RESULTS: Circ_0003892 expression was raised in PTC tissues and cells, which was significantly interrelated with larger tumor size and extrathyroidal extension in PTC sufferers. Overexpression of circ_0003892 significantly promoted the malignant biological behaviors of PTC cells. Additionally, miR-326 was a downstream target of circ_0003892, and miR-326 overexpression weakened the promoting effect of circ_0003892 overexpression on the malignant progression of PTC. MiR-326 specifically inhibited LASP1. Circ_0003892 positively regulated LASP1 expression by targeting miR-326. CONCLUSION: Circ_0003892 up-regulates LASP1 expression and facilitates PTC progression via competitively binding to miR-326.

PDA modified NIR-II NaEr0.8Yb0.2F4nanoparticles with high photothermal effect.

Polydopamine (PDA)-modified NaEr0.8Yb0.2 F4nanoparticles were synthesized, with strong NIR-II emission, quantum yield of 29.63%, and excellent photothermal performance. Crystal phases and microstructures are characterized. Optical properties such as absorption, NIR-II emission, and light stability are studied, and the luminescence mechanism is discussed in detail. Key factors in NIR-II imaging were evaluated in fresh pork tissue, including penetration depth, spatial resolution, and signal-to-noise ratio (SNR). A high penetration depth of 5 mm and a high spatial resolution of 1 mm were detected. Mice are imaged in vivo afterintravenousinjection. Due to the accumulation of nanoparticles in the liver, high image quality with an SNR of 5.2 was detected in the abdomen of KM mice with hair. The photothermal conversion effect of PDA-modified NPs was twice that of the reported material. These NIR-II nanoparticles have superior optical properties, high photothermal efficiency and low cytotoxicity, and are potential fluorescent probes for further disease diagnosis and treatment.

Long non-coding RNA AGAP2-AS1 promotes cell proliferation and invasion through regulating miR-193a-3p/LOXL4 axis in laryngeal squamous cell carcinoma.

Laryngeal squamous cell carcinoma (LSCC) is an aggressive malignancy with highly mortality rate. Long non-coding RNA (lncRNA) AGAP2-AS1 is an identified oncogene in several types of cancers. However, the role of AGAP2-AS1 in LSCC remains unclear. The expression levels of AGAP2-AS1 in LSCC tissues and cell lines were measured using qRT-PCR. AGAP2-AS1 was knocked down in LSCC cells through transfection with siRNA-AGAP2-AS1. Cell proliferation and invasion were detected using MTT and transwell assays. Dual-luciferase reporter gene assay was performed to confirm the interaction with AGAP2-AS1 and downstream genes. Our results showed that AGAP2-AS1 expression was remarkably increased in human LSCC tissues and cell lines. Knockdown of AGAP2-AS1 significantly inhibited the proliferation and invasion of LSCC cells. In addition, AGAP2-AS1 sponged miR-193a-3p and regulated its expression in LSCC cells. Inhibition of miR-193a-3p reversed the effects of AGAP2-AS1 knockdown on LSCC cells. Furthermore, Lysyl oxidase-like 4 (LOXL4) was a target gene of miR-193a-3p and the role of miR-193a-3p was mediated by LOXL4. In conclusion, these findings suggest that knockdown of AGAP2-AS1 inhibited the proliferation and invasion of LSCC cells through regulating the miR-193a-3p/LOXL4 axis.

Three-dimensional quantitative assessment of myocardial infarction via multimodality fusion imaging: methodology, validation, and preliminary clinical application.

BACKGROUND: The precise assessment of myocardial infarction (MI) is crucial both for therapeutic interventions in old MI and the development of new and effective techniques to repair injured myocardium. A novel method was developed to assess left ventricular (LV) quantitatively infarction through three-dimensional (3D) multimodality fusion based on computed tomography angiography (CTA) and technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) single-photon emission computed tomography (SPECT) images. This study sought to develop a 3D quantitative method for MI for pre-clinical study and clinical application. METHODS: Three months after the MI models were established in 20 minipigs, CTA and SPECT images were acquired separately, which were then aligned automatically with the constraints of the shape and the whole heart and LV myocardium position. Infarct ratios were quantified based on the 3D fusion images. The quantitative assessment was then experimentally validated via an ex vivo histology analysis using triphenyl-tetrazolium-chloride staining and subsequently applied to post-MI patients (n=8). RESULTS: The location of an infarct identified by the SPECT was consistent with that identified by an ex vivo heart in a 3D space. Infarct size determined by CTA-SPECT was correlated with infarct size assessed by triphenyl-tetrazolium-chloride pathology {27.6% [interquartile range (IQR) 17.1-34.7%] vs. 24.1% (IQR 14.7-32.5%), r2=0.99, P<0.01}. In clinical cases, the CTA-SPECT 3D fusion quantitative results were significantly correlated with the quantitative perfusion SPECT results (r=0.976, P<0.01). CONCLUSIONS: The proposed 3D fusion quantitative assessment method provides reliable and intuitive evaluations of infarction. This novel quantification technique enables whole heart quantification for the pre-operation evaluation and post-diagnosis management of old MI patients. It could also be applied to the design of 3D-printed cardiac patches.

A Thrombin-Responsive Nanoprobe for In Vivo Visualization of Thrombus Formation through Three-Dimensional Optical/Computed Tomography Hybrid Imaging.

Early spontaneous detection of thrombin activation benefits precise theranostics for thrombotic vascular disease. Herein, a thrombin-responsive nanoprobe conjugated by a FITC dye, PEGylated Fe3O4 nanoparticles, and a thrombin-sensitive peptide (LASG) was constructed to visualize thrombin activation and subsequent thrombosis in vivo. The FITC dye was linked to the LASG coated on the Fe3O4 nanoparticles for sensing the thrombin activity via the Förster resonance energy transfer effect. In vitro fluorescence imaging showed that the fluorescence signal intensity increased significantly after incubation with thrombin in contrast to that of the control group (p < 0.05), and the signal intensity was enhanced with the increase in thrombin concentration. Further in vivo fluorescence imaging also revealed that the signal elevated markedly in the left common carotid artery (LCCA) lesion of the mice thrombosis model after nanoprobe injection, in contrast to that of the control + nanoprobe group (p < 0.05). Moreover, the thrombin inhibitor bivalirudin could decrease the filling defect of the LCCA. Three-dimensional fusion images of micro-CT and fluorescence confirmed that filling defects in the LCCA were nicely colocalized with fluorescence signal caused by nanoprobes. The nanoplatform based on a thrombin-activatable visualization system could provide smart responsive and dynamic imaging of thrombosis in vivo.

A Nanometer-Sized Graphite/Boron-Doped Diamond Electrochemical Sensor for Sensitive Detection of Acetaminophen.

A boron-doped diamond (BDD) has been widely used as an outstanding electrode for constructing high-performance electrochemical biosensors. In this paper, we fabricated a novel electrode combined of nanometer-sized graphite-BDD film (NG-BDD) by chemical vapor deposition. The nanometer-sized graphite (NG) is formed on the (111) facet of BDD via converting an sp3 diamond structure to an sp2 graphitic phase at high temperature in boron-rich ambient. The electrode was characterized by means of scanning electron microscopy, Raman spectroscopy, X-ray diffraction, and X-ray photoelectron spectroscopy. This NG-BDD was performed as an electrode of electrochemical biosensor to detect trace acetaminophen (APAP) accurately. Cyclic voltammetry and differential normal pulse voltammetry are used to investigate the overall performance of the electrochemical device. The sensor has a linear electrochemical response to APAP in the concentration range of 0.02-50 µM, and the detection limit is estimated to be as low as 5 nM. The research has resulted in a solution of constructing a reusable NG-BDD sensor to detect APAP with stability and show potential in extensive application.

Long non-coding RNA AGAP2-AS1 promotes proliferation and metastasis in papillary thyroid cancer by miR-628-5p/KLF12 axis.

Long non-coding RNA (lncRNA) AGAP2-AS1 acts as an oncogene in several types of cancers. However, the role and mechanism of AGAP2-AS1 in papillary thyroid carcinoma (PTC) remain unclear. Thus, in this study, we aimed to explore the role of AGAP2-AS1 in PTC. Our results showed that AGAP2-AS1 was significantly upregulated in PTC tissues. Knockdown of AGAP2-AS1 inhibited the proliferation, migration and invasion of PTC cells. In vivo experiment showed that AGAP2-AS1 knockdown inhibited the tumorigenesis of PTC. MiR-628-5p was found to act as a target miRNA of AGAP2-AS1 in PTC. The expression level of miR-628-5p in PTC tissues was negatively associated with that of AGAP2-AS1. Inhibition of miR-628-5p attenuated the effects of AGAP2-AS1 knockdown on PTC. Moreover, miR-628-5p directly bound to the 3'UTR of KLF12 and inhibited the expression of KLF12. Knockdown of KLF12 enhanced the inhibitory effects of miR-628-5p on PTC cell proliferation and metastasis. In conclusion, these findings indicated that AGAP2-AS1 exerted an oncogenic role in PTC progression and metastasis. The effects of AGAP2-AS1 might be mediated by the regulation of miR-628-5p/KLF12 axis.