Background: Thyroid cancer is a frequent endocrine tumor in women. It is of great significance to investigate the molecular mechanism of progression of thyroid cancer.Methods: Gene expression data set and clinical data were downloaded from The Cancer Genome Atlas database for differential expression analysis. The triplet of downstream transcription factors (TFs) and modulatory genes of target lncRNA in thyroid cancer was predicted by the lncMAP database. mRNA and protein expression of lncRNA LBX2-AS1, RARα, and FSTL3 were detected by qRT-PCR and western blot. The localization of lncRNA LBX2-AS1 in cells was tested by Fluorescence in situ hybridization assay. The RNA immunoprecipitation assay was applied to verify the binding relationship between lncRNA LBX2-AS1 and FSTL3. ChIP and dual-luciferase assays were used to prove the binding relationship between RARα and FSTL3. Cell function experiments were used to test cell proliferation, migration and invasion in each treatment group. The role of lncRNA LBX2-AS1 in thyroid cancer progression was also confirmed in nude mice.Results: Bioinformatics analysis indicated that lncRNA LBX2-AS1, RARα, FSTL3 were remarkably fostered in thyroid cancer tissue, and LBX2-AS1 was evidently correlated with clinical features. The LncMAP triplet prediction showed that LBX2-AS1 recruited TF RARα to modulate FSTL3. RIP assay confirmed that LBX2-AS1 was prominently enriched on RARα. ChIP and dual-luciferase report assays unveiled that RARα bound to the promoter region of FSTL3 and functioned as a TF. Cell function experiments uncovered that LBX2-AS1 boosted the progression of thyroid cancer. The rescue experiments showed that LBX2-AS1 recruited the TF RARα to hasten the transcription activity of FSTL3 and thus promoted the development of thyroid cancer.Conclusion: The integrative results demonstrated that LBX2-AS1 activated FSTL3 by binding to TF RARα to hasten proliferation, migration and invasion of thyroid cancer.
The present study analyzed the ability of metabolic burden indices from 18 F-fluorodeoxyglucose (18 F-FDG) positron emission tomography/computed tomography (PET/CT) to predict tumor recurrence following orthotopic liver transplantation (OLT) in patients with hepatocellular carcinoma (HCC). Seven major metabolic indices were measured by 18 F-FDG PET/CT in 93 patients with HCC, prior to OLT. The Mann-Whitney U test was then used to predict the association of metabolic indices, including the maximum standardized uptake value (SUVmax), tumor-to-mediastinum SUV ratio, tumor-to-normal-liver SUV ratio, SUV normalized to lean body mass metabolic tumor volume (MTV), total lesion glycolysis (TLG) and uptake-volume product (UVP), with the recurrence risk. The Deauville-like scoring system was used to quantify the recurrence risk. Univariate and multivariable Cox regression models were performed to determine survival rate. The results showed that Deauville-like score (PET-negative vs.-positive), MTV (cutoff value, 13.36), TLG (cutoff value, 62.21) and UVP (cutoff value, 66.60) had high prediction performance for tumor recurrence (P<0.05). TLG had the highest receiver operating characteristics area under the curve of 0.725. Among the clinical factors, high level of α-fetoprotein (AFP, ≥144 ng/ml), Milan criteria, tumor number (>3), involvement of both right and left lobes, and tumor size (>5 cm) were found to be significant predictors of tumor recurrence. Patients in the low metabolic group had longer recurrence-free survival (RFS) times compared with those in the high metabolic group, regardless of whether they met the Milan criteria or not. AFP, uptake-volume product according the SUV mean of mediastinum (UVP-M), Milan criteria, lymph node metastasis, and the number of tumors were significant prognostic factors for RFS (P<0.05) in both univariate and multivariate survival analyses. Additionally, the MVI was a significant prognostic factor based on univariate survival analyses. Overall, the present study demonstrated the metabolic burden indices measured by PET/CT, Deauville-like score, MTV, TLG and UVP as significant prognostic factors in patients with HCC following OLT. The combination of metabolic indices measured by PET/CT and the existing criteria, such as the Milan criteria, may play an important role in evaluating the suitability of OLT in specific patients.
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Necroptosis is a newly identified programmed cell death associated with the biological process of various cancers, including esophageal carcinoma (ESCA). Meanwhile, the dysregulation of long non-coding RNAs (lncRNAs) is greatly implicated in ESCA progression and necroptosis regulation. However, the lncRNAs involved in regulating necroptosis in ESCA are still unclear. In this study, we aim to explore the expression profile of necroptosis-related lncRNAs (NRLs), and evaluate their roles in ESCA prognosis and treatment. In the present study, 198 differentially expressed NRLs were identified between the ESCA and adjacent normal tissues through screening the data extracted from the Cancer Genome Atlas (TCGA) database. And, a prognostic panel consisting of 6 NRLs was constructed using the LASSO algorithm and multivariate Cox regression analysis. The ESCA patients with high risks had a markedly reduced survival time and higher mortality prevalence. Moreover, C-index of 6 NRLs-panel was superior to 48 published prognostic models based on lncRNAs or mRNAs for ESCA. There were significant differences between the high-risk and low-risk groups in tumor-related pathways, genetic mutations, and drug sensitivity responses. In vitro analysis revealed that inhibition of PVT1 impeded the proliferation, migration, and colony formation of ESCA cells, increased the expressions of p-RIP1 and p-MLKL and promoted necroptosis. By contrast, PVT1 overexpression resulted in a decrease in necroptotic cell death events, thus promoting tumor progression. Collectively, the established 6-NRLs panel was a promising biomarker for the prognostic prediction of ESCA. Moreover, our current findings provided potential targets for individualized therapy for ESCA patients.
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