BackgroundLung cancer remains the top contributor to cancer-related mortality worldwide. Long non-coding RNAs (lncRNAs) have been reported to participate in normal development and tumorigenesis. LncRNA nuclear enriched abundant transcript 1 (NEAT1) is highly expressed in lung cancer and promotes lung cancer cell proliferation and migration. However, the upstream regulatory mechanism still needs investigation.MethodsIn the present study, we investigated the upstream regulators and mechanisms of NEAT1 expression disorders. We first examined NEAT1 expression in lung adenocarcinoma tissues and its correlation with clinic features in patient with lung adenocarcinoma; next, the detailed function of NEAT1 in lung cancer cell proliferation and migration was assessed. To investigate whether NF-κB acts as a transcription factor of NEAT1 to activate its expression, we validated the combination between NF-κB and NEAT1, and NF-κB regulation of NEAT1 upon LPS stimulation. Further, the effect of NF-κB upstream regulator, TLR4, on NEAT1 expression upon LPS stimulation was examined. Galectin-3 reportedly serves as a ligand of TLR4 and promotes TLR4, MyD88 and p-p65 expression; we investigated whether Galectin-3 could modulate lung adenocarcinoma cell proliferation and migration through TLR4/NF-κB/NEAT1. Finally, the expression and correlation of the above factors in lung adenocarcinoma tissues was validated.ResultsNEAT1 is highly expressed in lung adenocarcinoma tissues and promotes lung cancer cell proliferation and migration. NF-κB binds to NEAT1 promoter to activate NEAT1 expression after LPS-stimulated p65 nucleus translocation. LPS stimulation activates TLR4 signaling, followed by downstream NF-κB activation, and ultimately NEAT1 expression activation. Galectin-3 activates TLR4 signaling thus affecting lung cancer cell proliferation and migration through TLR4/NF-κB/NEAT1. Galectin-3 and TLR4 expression are abnormally up-regulated in lung adenocarcinoma tissues, and positively correlated with NEAT1 expression.ConclusionWe confirmed that Galectin-3 as a ligand of TLR4 induced TLR4 signaling activation in lung adenocarcinoma cells, thereby activating downstream p65 nucleus translocation, promoting NEAT1 expression, and finally affecting lung adenocarcinoma cell proliferation and migration. Inhibiting Galectin-3-induced TLR4 signaling activation, thus to reduce p65-activated NEAT1 expression might be a promising strategy of suppressing lung adenocarcinoma cell proliferation and migration.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-4461-z) contains supplementary material, which is available to authorized users.

Background: The gene encoding the E3 ubiquitin ligase substrate-binding adaptor SPOP is frequently mutated in primary prostate cancer, but how SPOP mutations contribute to prostate cancer pathogenesis remains poorly understood. Stress granules (SG) assembly is an evolutionarily conserved strategy for survival of cells under stress, and often upregulated in human cancers. We investigated the role of SPOP mutations in aberrant activation of the SG in prostate cancer and explored the relevanve of the mechanism in therapy resistance. Methods: We identified SG nucleating protein Caprin1 as a SPOP interactor by using the yeast two hybrid methods. A series of functional analyses in cell lines, patient samples, and xenograft models were performed to investigate the biological significance and clinical relevance of SPOP regulation of SG signaling in prostate cancer. Results: The cytoplasmic form of wild-type (WT) SPOP recognizes and triggers ubiquitin-dependent degradation of Caprin1. Caprin1 abundance is elevated in SPOP-mutant expressing prostate cancer cell lines and patient specimens. SPOP WT suppresses SG assembly, while the prostate cancer-associated mutants enhance SG assembly in a Caprin1dependent manner. Knockout of SPOP or expression of prostate cancer-associated SPOP mutants conferred resistance to death caused by SG inducers (e.g. docetaxel, sodium arsenite and H 2 O 2) in prostate cancer cells. Conclusions: SG assembly is aberrantly elevated in SPOP-mutated prostate cancer. SPOP mutations cause resistance to cellular stress induced by chemtherapeutic drug such as docetaxel in prostate cancer.

Background: The purpose of this study was to evaluate the factors associated with lateral lymph node metastasis (LLNM) in patients with papillary thyroid carcinoma (PTC), and to develop two web-based nomograms that predict the probability of level-II and level-III/IV LLNM in these patients.Methods: The records of 653 patients with PTC were retrospectively reviewed. Univariate and multivariate analyses were performed to identify risk factors associated with LLNM in 460 patients ("derivation group").Two models [including and excluding the subregions of central lymph node metastasis (CLNM)] were used to predict the probability of level-II LLNM; the same two models were also used for level-III/IV LLNM.Model performance was assessed using receiver operating characteristic (ROC) analysis and decision curve analysis (DCA) in 193 patients ("validation group"). Two web-based nomograms were established.Results: Increased tumor size, a tumor in the upper lobe, and prelaryngeal and ipsilateral paratracheal lymph node metastasis (LNM) were significantly associated with level-II LNM (P<0.05). Increased tumor size, a tumor in the upper lobe, and certain subregions of CLNM were associated with level-III/IV LNM (P<0.05). Use of ROC analysis of each model indicated that including subgroups of CLNM led to better model performance than excluding these subgroups. We quantified the benefit of each model by using DCA analysis in the validation group.Conclusions: Our web-based nomograms provide quantification of risk for LLNM in patients with PTC before and during surgery.