BackgroudAccumulating evidences indicate that circular RNAs (circRNAs), a class of non-coding RNAs, play important roles in tumorigenesis. However, the function of circRNAs in hepatocellular cancer (HCC) is largely unknown.MethodsWe performed circRNA microarrays to identify circRNAs that are aberrantly expressed in HCC tissues. Expression levels of a significantly upregulated circRNA, circFBLIM1, was detected by quantitative real-time PCR (qRT-PCR) in HCC cell lines and tissues. Then, we examined the functions of circFBLIM1 in HCC by cell proliferation, apoptosis, invasion and mouse xenograft assay. In addition, luciferase assay and RNA immunoprecipitation (RIP) assay were used to explore the miRNA sponge function of circFBLIM1 in HCC.ResultsMicroarray analysis and qRT-PCR verified a circRNA termed circFBLIM1 that was upregulated in HCC tissues and cell lines. Knockdown of circFBLIM1 inhibited proliferation, invasion and promoted apoptosis in HCC. Via luciferase reporter assays, circFBLIM1 and FBLIM1 were observed to directly bind to miR-346. Subsequent experiments showed that circFBLIM1 and FBLIM1 regulated the expression of each other by sponging miR-346.ConclusionsTaken together, we conclude that circFBLIM1 may function as a competing endogenous RNA (ceRNA) to regulate FBLIM1 expression through sponging miR-346 to exert regulatory functions in HCC. circFBLIM1 may be a diagnostic biomarker and potential target for HCC therapy.

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Abstract. Thyroid cancer is the most frequently occurring type of endocrine tumor, with a rapidly increasing incidence rate. MicroRNA (miR)-574-5p is a candidate oncogene in various types of cancer. The present study identified that miR-574-5p affected the cell cycle distribution and apoptosis of BCPAP and FTC133 thyroid cancer cells via β-catenin/Wnt signaling by targeting Quaking proteins (QKIs). An MTT assay demonstrated that the knockdown of miR-574-5p suppressed the proliferation of the thyroid cancer cells. Fluorescence-activated cell sorting analysis demonstrated that the inhibition of miR-574-5p induced the G 1 /S phase arrest and apoptosis of the cells. Reverse transcription-quantitative polymerase chain reaction and western blot analyses revealed that the knockdown of miR-574-5p significantly upregulated the mRNA and protein expression levels of QKIs. Furthermore, western blot analysis identified that the knockdown of miR-574-5p also repressed the Wnt/β-catenin pathway via downregulating the expression of β-catenin, cyclin D1 and survivin, and upregulating the phosphorylation of β-catenin. The further depletion of QKIs in combination with the knockdown of miR-574-5p not only increased the expression of β-catenin, cyclin D1 and survivin, but also rescued the apoptosis of thyroid cancer cells induced by the miR-574-5p knockdown. In conclusion, these findings indicated that the aberrant upregulation of miR-574-5p may be oncogenic, through regulating the Wnt/β-catenin pathway by targeting QKIs.

Abstract. The angiopoietin 1 (Ang1)/angiopoietin receptor (Tie2) signaling pathway may have a notable role in the pathogenesis of inflammatory diseases. The abnormal expression of angiopoietin 1 and Tie2 has also been reported in various malignant tumors, including papillary thyroid carcinoma (PTC). However, the role and mechanism of the Ang1/Tie2 pathway in the progression of PTC remains unclear. Therefore, the aims of the present study were to clarify this. Significantly high expression levels of Ang1 and Tie2 were observed in PTC tissues and cell lines. Furthermore, MTT and wound-healing assays revealed that the Ang1-mediated stimulation of human PTC cells resulted in increased proliferation and migration. Conversely, the downregulation of Tie2 levels using short hairpin RNA targeted at Tie2 abrogated the Ang1-mediated effect on cell proliferation and migration. In studying the expression of phosphoinositide-3 kinase (PI3K)/RAC serine/threonine-protein kinase (Akt) pathway, the upregulation of Ang1/Tie2 was found to be associated with the activation of the PI3K/Akt pathway in PTC. In conclusion, the data from the present study indicated that the Ang1/Tie2 induces PTC oncogenesis via the PI3K/Akt pathway, providing novel insights into human PTC therapy. IntroductionPapillary thyroid carcinoma (PTC) is the most prevalent histological thyroid carcinoma subtype, accounting for ~80% of cases (1,2). Although recent advances in diagnosis and treatment strategies have been made in clinical and experimental oncology, ≤30% of patients present with local/regional recurrence or distant metastasis within 10 years (2,3). Thus, the elucidation of the molecular mechanisms underlying PTC progression is urgently required in order to develop effective diagnostic, prognostic and therapeutic strategies.Receptor tyrosine kinases are cell surface proteins that transduce signals from extracellular growth factors intracellularly, to elicit biological responses (4). Receptor tyrosine kinases act as potent oncoproteins and are abnormally expressed in a number of cancer types, including gliomas (5). Angiopoietin-1 (Ang1) receptor (TEK, also known as Tie2) is a receptor tyrosine kinase that was identified as an endothelial-cell-specific receptor with a critical role in the modulation of vasculogenesis and remodeling (6). Tie2 expression occurs, and is partially maintained, during differentiation in human neural stem cells (7), but not in mature neurons (8). Dysregulated Tie2 expression has also been observed in several tumor tissues, including oral squamous cell carcinoma, breast, gastric, leukemia and thyroid cancer (9-13). These studies revealed that Tie2 expression is associated with the identification and prognosis of these cancer types (12). Ang1 is a secreted ligand for Tie2 that maintains vascular plasticity, perturbations in which can contribute to abnormal vascular growth (4). Daly et al (6) revealed that Ang2 functions as a Tie2 agonist in tumor models, limiting the effects of VEGF inhibition (6). Mitsutake et al (13) revealed ...

Hepatocellular carcinoma (HCC) occurs mainly in chronically diseased livers following hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Early detection and diagnosis of HCC would be of great clinical benefit. In this study, we used a random phage display peptide library and sera from early-stage primary HCC patients (n = 30) to screen potential serum biomarkers for early primary HCC. Age- and sex-matched patients with HBV and/or HCV infection were used as controls. In the screening phase, 19 out of 20 randomly selected phage clones exhibited specific reaction with purified sera IgG from early primary HCC patients, among them 14 coming from the same phage clone with inserted peptidesequence RGWCRPLPKGEG (named HC1). In the validation phase, phage ELISA results showed that the positive reaction rate of the HC1 phage clone was 91.4% with the early HCC group (n = 70), significantly higher than that with the HBV infection group (20.0%) (n = 70), the HCV infection group (12.9%) (n = 70), the HBV + HCV infection group (24.3%) (n = 70), the cirrhosis group (17.1%) (n = 70), and the healthy control group (10.0%) (n = 70). In conclusion, the HC1 mimic peptide showed high diagnostic validity for early primary HCC, and thereby could be a candidate serum biomarker for early primary HCC.

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Background: The optimal extent of therapeutic lateral neck dissection (LND) in the management of N1b papillary thyroid microcarcinoma (PTMC) is still under debate in clinical practice. In this light, our study aims to explore the incidence, patterns, and predictive factors of the lateral multiple-level metastasis in N1b PTMC patients. Methods: The clinical records of 142 patients diagnosed with N1b PTMC who underwent therapeutic LND from July 2015 to November 2018 at our institution were retrospectively reviewed. Univariate and multivariate analyses were conducted to examine the predictive factors associated with lateral multiple-level metastasis. The recurrence-free survival was analyzed and confirmed by Kaplan–Meier plots and log-rank test. Results: The overall frequency of lateral multiple-level metastasis was 50.7% in N1b PTMC patients, and two-level to four-level simultaneous metastasis were present in 26.8, 17.6, and 6.3% patients, respectively. Extrathyroidal extension (ETE) (OR = 5.79, 95% CI, 1.36–24.59; P = 0.017) and the central metastatic lymph node ratio (CLNR) with values equal or higher than 0.61 (OR = 6.18, 95% CI, 2.53–15.09; P < 0.001) served as independent predictors of multiple-level metastasis in N1b PTMC patients. Moreover, locoregional recurrence was significantly higher in the selective neck dissection (SND) group compared to the modified radical neck dissection (MRND) one (HR = 3.65, 95% CI, 1.11–12.00; P = 0.03). Conclusion: Our results show that the lateral multiple-level metastasis was relatively common, and we suggest MRND to be considered for N1b PTMC patients with ETE or CLNR equal or higher than 0.61.