Early Coagulation Disorder Is Associated With an Increased Risk of Atrial Fibrillation in Septic Patients.

Background: Atrial fibrillation (AF) and coagulation disorder, two common complications of sepsis, are associated with the mortality. However, the relationship between early coagulation disorder and AF in sepsis remains elusive. This study aimed to evaluate the interaction between AF and early coagulation disorder on mortality. Methods: In this retrospective study, all data were extracted from the Medical Information Mart for Intensive Care III (MIMIC-III) database. Septic patients with coagulation tests during the first 24 h after admission to intensive care units (ICUs) meeting study criteria were included in the analysis. Early coagulation disorder is defined by abnormalities in platelet count (PLT), international normalized ratio (INR) and activated partial thromboplastin time (APTT) within the first 24 h after admission, whose score was defined with reference to sepsis-induced coagulopathy (SIC) and coagulopathy. Patients meeting study criteria were divided into AF and non-AF groups. Results: In total, 7,528 septic patients were enrolled, including 1,243 (16.51%) with AF and 5,112 (67.91%) with early coagulation disorder. Compared with patients in the non-AF group, patients in the AF group had higher levels of INR and APTT (P < 0.001). Multivariable logistic regression analyses showed that stroke, early coagulation disorder, age, gender, congestive heart failure (CHF), chronic pulmonary disease, renal failure, and chronic liver disease were independent risk factors for AF. In addition, AF was related to in-hospital mortality and 90-day mortality. In the subgroup analysis stratified by the scores of early coagulation disorder, AF was associated with an increased risk of 90-day mortality when the scores of early coagulation disorder were 1 or 2 and 3 or 4. Conclusion: In sepsis, coagulation disorder within the first 24 h after admission to the ICUs is an independent risk factor for AF. The effect of AF on 90-day mortality varies with the severity of early coagulation disorder.

Cellular senescence in hepatocellular carcinoma induced by a long non-coding RNA-encoded peptide PINT87aa by blocking FOXM1-mediated PHB2.

Rationale: Recently, long non-coding RNAs (lncRNAs), known to be involved in human cancer progression, have been shown to encode peptides with biological functions, but the role of lncRNA-encoded peptides in cellular senescence is largely unexplored. We previously reported the tumor-suppressive role of PINT87aa, a peptide encoded by the long intergenic non-protein coding RNA, p53 induced transcript (LINC-PINT). Here, we investigated PINT87aa's role in hepatocellular carcinoma (HCC) cellular senescence. Methods: We examined PINT87aa and truncated PINT87aa functions in vitro by monitoring cell proliferation and performed flow cytometry, senescence-associated ß-galactosidase staining, JC-1 staining indicative of mitochondrial membrane potential, the ratio of the overlapping area of light chain 3 beta (LC3B) and mitochondrial probes and the ratio of lysosomal associated membrane protein 1 (LAMP1) overlapping with cytochrome c oxidase subunit 4I1 (COXIV) denoting mitophagy. PINT87aa and truncated PINT87aa functions in vivo were verified by subcutaneously transplanted tumors in nude mice. The possible binding between PINT87aa and forkhead box M1 (FOXM1) was predicted through structural analysis and verified by co-immunoprecipitation and immunofluorescence co-localization. Rescue experiments were performed in vivo and in vitro following FOXM1 overexpression. Further, chromatin immunoprecipitation, polymerase chain reaction, and dual-luciferase reporter gene assay were conducted to validate FOXM1 binding to the prohibitin 2 (PHB2) promoter. Results: PINT87aa was significantly increased in the hydrogen peroxide-induced HCC cell senescence model. Overexpression of PINT87aa induced growth inhibition, cellular senescence, and decreased mitophagy in vitro and in vivo. In contrast, FOXM1 gain-of-function could partially reduce the proportion of senescent HCC cells and enhance mitophagy. PINT87aa overexpression did not affect the expression of FOXM1 itself but reduced that of its target genes involved in cell cycle and proliferation, especially PHB2, which was involved in mitophagy and transcribed by FOXM1. Structural analysis indicated that PINT87aa could bind to the DNA-binding domain of FOXM1, which was confirmed by co-immunoprecipitation and immunofluorescence co-localization. Furthermore, we demonstrated that the 2 to 39 amino acid truncated form of the peptide exerted effects similarly to the full form. Conclusion: Our study established the role of PINT87aa as a novel biomarker and a key regulator of cellular senescence in HCC and identified PINT87aa as a potential therapeutic target for HCC.

Fork head box M1 regulates vascular endothelial growth factor-A expression to promote the angiogenesis and tumor cell growth of gallbladder cancer.

BACKGROUND: Gallbladder cancer (GBC) is an aggressive type of biliary tract cancer that lacks effective therapeutic targets. Fork head box M1 (FoxM1) is an emerging molecular target associated with tumor progression in GBC, and accumulating evidence suggests that vascular endothelial growth factor (VEGF) promotes various tumors by inducing neoangiogenesis. AIM: To investigate the role of FoxM1 and the angiogenesis effects of VEGF-A in primary GBC. METHODS: Using immunohistochemistry, we investigated FoxM1 and VEGF-A expression in GBC tissues, paracarcinoma tissues and cholecystitis tissues. Soft agar, cell invasion, migration and apoptosis assays were used to analyze the malignant phenotype influenced by FoxM1 in GBC. Kaplan-Meier survival analysis was performed to evaluate the impact of FoxM1 and VEGF-A expression in GBC patients. We investigated the relationship between FoxM1 and VEGF-A by regulating the level of FoxM1. Next, we performed MTT assays and Transwell invasion assays by knocking out or overexpressing VEGF-A to evaluate its function in GBC cells. The luciferase assay was used to reveal the relationship between FoxM1 and VEGF-A. BALB/c nude mice were used to establish the xenograft tumor model. RESULTS: FoxM1 expression was higher in GBC tissues than in paracarcinoma tissues. Furthermore, the high expression of Foxm1 in GBC was significantly correlated with a malignant phenotype and worse overall survival. Meanwhile, high expression of FoxM1 influenced angiogenesis; high expression of FoxM1 combined with high expression of VEGF-A was related to poor prognosis. Attenuated FoxM1 significantly suppressed cell proliferation, transfer and invasion in vitro. Knockdown of FoxM1 in GBC cells reduced the expression of VEGF-A. Luciferase assay showed that FoxM1 was the transcription factor of VEGF-A, and knockdown VEGF-A in FoxM1 overexpressed cells could partly reverse the malignancy phenotype of GBC cells. In this study, we found that FoxM1 was involved in regulation of VEGF-A expression. CONCLUSION: FoxM1 and VEGF-A overexpression were associated with the prognosis of GBC patients. FoxM1 regulated VEGF-A expression, which played an important role in the progression of GBC.

Linc01559 Served as a Potential Oncogene and Promoted Resistance of Hepatocellular Carcinoma to Oxaliplatin by Directly Sponging miR-6783-3p.

BACKGROUND: Oxaliplatin (L-OHP)-based chemotherapy, such as FOLFOX4 (5-fluorouracil, leucovorin, and L-OHP), improves the prognosis of patients with late-stage Hepatocellular Carcinoma (HCC). However, the development of resistance to L-OHP leads to the failure of chemotherapy. The aim of this study was to investigate the role of linc01559 and miR-6783-3p in regulating resistance to L-OHP. METHODS: Quantitative reverse transcription-polymerase chain reaction was used to determine the expression profile. The Cell Counting Kit-8 test and wound healing assay were also used. Dual-luciferase reporter gene assay, RNA pull-down assay, and RNA immunoprecipitation were used to evaluate the interaction between linc01559 and miR-6783-3p. RESULT: linc01559 expression was associated with response to FOLFOX4, as well as miR-1343-3p and miR- 6783-3p expression in vivo. A nomogram, including linc01559 and miR-1343-3p, precisely and accurately predicted the overall survival of patients with HCC. Regarding the in vitro tests, linc01559 showed higher expression in L-OHP-resistant cell lines, whereas miR-6783-3p was downregulated. Knockdown of linc01559 led to decreased proliferation and migration ability, and increased expression of miR-6783-3p; however, it did not influence the expression of miR-1343-3p. We also found that linc01559 directly interacted with miR-6783-3p. Furthermore, linc01559 and miR-6783-3p regulated the viability of L-OHP-resistant cells following treatment with L-OHP. CONCLUSION: linc01559 promoted the proliferation of HCC by sponging miR-6783-3p. This suggests that linc01559/miR-6783-3p may be key factors in regulating resistance and response to L-OHP. Moreover, they may be potential therapeutic targets for improving sensitivity to L-OHP in patients with HCC.

[Erratum] Long non-coding RNA KCNQ1OT1 mediates the growth of hepatocellular carcinoma by functioning as a competing endogenous RNA of miR-504.

Following the publication of this article, the authors have realized that Table I was not included with the printed version of the article, although it was referenced in the text. Subsequently, it has been determined that a processing error or oversight must have been made during the pre-press stages. Table I, as it should have appeared in this paper, is shown in the next page. We apologize to the authors for this omission, and regret the inconvenience that this has caused.[the original article was published in International Journal of Oncology 52: 1603-1612, 2018; DOI: 10.3892/ijo.2018.4313].

Simplified nomograms based on platelet-associated models for survival prediction in Asian hepatocellular carcinoma patients after surgery.

BACKGROUND & AIMS: Accumulating evidence showed platelets were closely related to hepatocellular carcinoma (HCC) prognosis. We here aimed to develop two simple-to-use nomograms based on the PLT-associated modified models to refine prognostic prediction of Asian HCC. METHODS: The nomograms were established using 684 eligible Asian patients who received curative resection for HCC, among which 456 and 228 were randomly assigned to the derivation and validation cohorts, respectively. Univariate and multivariate Cox analyses in the derivation set were used to identify the independent prognostic factors of the hepatectomy patients as the nomogram variables. We evaluated the discrimination and calibration of the nomograms by concordance indexes (C-index), calibration plots and Kaplan-Meier curves. The discrimination ability of the PLT-based nomograms was compared with the conventional staging systems using time-dependent receiver operating characteristic (ROC) curves. RESULTS: The nomogram for overall survival (OS) estimation was comprised of MPV/PC [mean platelet volume/platelet count], SII [systemic immune-inflammation index], NPS [neutrophil-platelet score], PAPAS [platelet count/age/ALP/AFP/AST index] and S index. And the nomogram for recurrence-free survival (RFS) prediction was of NPS, PAPAS and S index. The C-indexes of the OS nomogram in the derivation and validation sets were 0.704 and 0.707, and those of the RFS nomogram were 0.668 and 0.703. The calibration plots fitted well. The survival curves showed great discriminatory powers. The area under the curve (AUC) of our nomograms were significantly larger than that of the three conventional models (P < 0.05). CONCLUSIONS: The two PLT-based nomograms were accurate in predicting the OS and RFS of Asian HCC patients after hepatectomy.

Seven-senescence-associated gene signature predicts overall survival for Asian patients with hepatocellular carcinoma.

BACKGROUND: Cellular senescence is a recognized barrier for progression of chronic liver diseases to hepatocellular carcinoma (HCC). The expression of a cluster of genes is altered in response to environmental factors during senescence. However, it is questionable whether these genes could serve as biomarkers for HCC patients. AIM: To develop a signature of senescence-associated genes (SAGs) that predicts patients' overall survival (OS) to improve prognosis prediction of HCC. METHODS: SAGs were identified using two senescent cell models. Univariate COX regression analysis was performed to screen the candidate genes significantly associated with OS of HCC in a discovery cohort (GSE14520) for the least absolute shrinkage and selection operator modelling. Prognostic value of this seven-gene signature was evaluated using two independent cohorts retrieved from the GEO (GSE14520) and the Cancer Genome Atlas datasets, respectively. Time-dependent receiver operating characteristic (ROC) curve analysis was conducted to compare the predictive accuracy of the seven-SAG signature and serum α-fetoprotein (AFP). RESULTS: A total of 42 SAGs were screened and seven of them, including KIF18B, CEP55, CIT, MCM7, CDC45, EZH2, and MCM5, were used to construct a prognostic formula. All seven genes were significantly downregulated in senescent cells and upregulated in HCC tissues. Survival analysis indicated that our seven-SAG signature was strongly associated with OS, especially in Asian populations, both in discovery and validation cohorts. Moreover, time-dependent ROC curve analysis suggested the seven-gene signature had a better predictive accuracy than serum AFP in predicting HCC patients' 1-, 3-, and 5-year OS. CONCLUSION: We developed a seven-SAG signature, which could predict OS of Asian HCC patients. This risk model provides new clinical evidence for the accurate diagnosis and targeted treatment of HCC.

IDH1 as a frequently mutated gene has potential effect on exosomes releasement by epigenetically regulating P2RX7 in intrahepatic cholangiocarcinoma.

Biliary tract cancers (BTCs) was heterogeneous and characterized by late diagnosis and fatal outcome. To identify new biomarkers for BTCs, we performed Robust Rank Aggreg (RRA) analysis and identified that IDH1 mutation was common in ICC, while IDH1R132C was the most frequent type. Moreover, we identified P2RX7 and other 45 genes as downregulated genes with hypermethylation in IDH1R132C mutated cells. The WGCNA results predicted that P2RX7 could influence cholangiocarcinoma by exosomes related manners. Finally, we confirmed that P2RX7 was downregulated in IDH1R132C mutated cells as well as the expression of CD9 and CD81 by experiments. In conclusion, IDH1R132C mutation was relatively prevalent in ICC. P2RX7 might be a potential downstream gene and it might be related to exosomes releasement.

Methane alleviates sepsis-induced injury by inhibiting pyroptosis and apoptosis: in vivo and in vitro experiments.

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. Methane has been reported to have anti-oxidative, anti-apoptotic and anti-inflammatory properties. We investigated the potential protective effects of methane on sepsis-induced injury and determined the related mechanisms. C57BL/6 mice received laparotomy with cecal ligation and puncture (CLP) to create a septic model, followed by methane-rich saline (MRS) treatment after CLP. MRS treatment improved the 5-day survival rate and organ functions and alleviated pathological damage of the mice, as well as reduced excessive inflammatory mediators, such as tumor necrosis factor-α and interleukin-6. MRS treatment also decreased the levels of oxidative stress index proteins, decreased the apoptosis of cells and inhibited nod-liker receptor protein (NLRP)3-mediated pyroptosis in the lung and intestine. In in vitro experiments, RAW264.7 and primary peritoneal macrophages were treated with lipopolysaccharide (LPS) plus adenosine-triphosphate (ATP) to induce inflammation and pyroptosis. Consistent with the in vivo results, methane-rich medium (MRM) treatment also reduced the levels of excessive inflammatory mediators, and decreased the levels of ROS, inhibited apoptosis and pyroptosis. Our results indicate that methane offers a protective effect for septic mice via its anti-inflammation, anti-oxidation, anti-pyroptosis and anti-apoptosis properties.

Combined eight-long noncoding RNA signature: a new risk score predicting prognosis in elderly non-small cell lung cancer patients.

The elderly are the majority of patients with non-small cell lung cancer (NSCLC). Compared to the overall population's predictive guidance, an effective predictive guidance for elderly patients can better guide patients' postoperative treatment and improve overall survival (OS) and disease-free survival (DFS). Recently, the long non-coding RNAs (lncRNAs) have been found to play an important role in predicting tumor prognosis. To identify potential lncRNAs to predict survival in elderly patients with NSCLC, in the present study, we chose 456 elderly patients with NSCLC and analyzed differentially expressed lncRNAs from four Gene Expression Omnibus (GEO) datasets (GSE30219, GSE31546, GSE37745 and GSE50081). We then constructed an eight-lncRNA formula to predict elderly patients' prognosis in NSCLC. Furthermore, we validated the prognostic values of the new risk model in two independent datasets, TCGA (n=670) and GSE31210 (n=130). Our data suggested a significant association between risk model and patients' prognosis. Finally, stratification analysis further revealed the eight-lncRNA signature was an independent factor to predict OS and DFS in stage I elderly patients from both the discovery and validation groups. Functional prediction revealed that 8 lncRNAs have potential effects on tumor immune processes such as lymphocyte activation and TNF production in NSCLC. In summary, our data provides evidence that the eight-lncRNA signature could serve as an independent biomarker to predict prognosis in elderly patients with NSCLC especially in elderly stage I patients.

Six-long non-coding RNA signature predicts recurrence-free survival in hepatocellular carcinoma.

BACKGROUND: Recent evidence shows that long non-coding RNAs (lncRNAs) are closely related to hepatogenesis and a few aggressive features of hepatocellular carcinoma (HCC). Increasing studies demonstrate that lncRNAs are potential prognostic factors for HCC. Moreover, several studies reported the combination of lncRNAs for predicting the overall survival (OS) of HCC, but the results varied. Thus, more effort including more accurate statistical approaches is needed for exploring the prognostic value of lncRNAs in HCC. AIM: To develop a robust lncRNA signature associated with HCC recurrence to improve prognosis prediction of HCC. METHODS: Univariate COX regression analysis was performed to screen the lncRNAs significantly associated with recurrence-free survival (RFS) of HCC in GSE76427 for the least absolute shrinkage and selection operator (LASSO) modelling. The established lncRNA signature was validated and developed in The Cancer Genome Atlas (TCGA) series using Kaplan-Meier curves. The expression values of the identified lncRNAs were compared between the tumor and non-tumor tissues. Pathway enrichment of these lncRNAs was conducted based on the significantly co-expressed genes. A prognostic nomogram combining the lncRNA signature and clinical characteristics was constructed. RESULTS: The lncRNA signature consisted of six lncRNAs: MSC-AS1, POLR2J4, EIF3J-AS1, SERHL, RMST, and PVT1. This risk model was significantly associated with the RFS of HCC in the TCGA cohort with a hazard ratio (HR) being 1.807 (95%CI [confidence interval]: 1.329-2.457) and log-rank P-value being less than 0.001. The best candidates of the six-lncRNA signature were younger male patients with HBV infection in relatively early tumor-stage and better physical condition but with higher preoperative alpha-fetoprotein. All the lncRNAs were significantly upregulated in tumor samples compared to non-tumor samples (P < 0.05). The most significantly enriched pathways of the lncRNAs were TGF-ß signaling pathway, cellular apoptosis-associated pathways, etc. The nomogram showed great utility of the lncRNA signature in HCC recurrence risk stratification. CONCLUSION: We have constructed a six-lncRNA signature for prognosis prediction of HCC. This risk model provides new clinical evidence for the accurate diagnosis and targeted treatment of HCC.

Prognostic predictors for patients with hepatocellular carcinoma receiving adjuvant transcatheter arterial chemoembolization.

OBJECTIVES: We aimed to confirm the clinical effectiveness of postoperative adjuvant transcatheter arterial chemoembolization (PA-TACE) in patients with hepatocellular carcinoma after liver resection, and further identify the patients who could benefit most from PA-TACE. PATIENTS AND METHODS: Propensity score matching at a ratio of 1 : 2 was used between hepatectomy patients with and without receiving PA-TACE. Kaplan-Meier analysis was performed to compare overall survival and recurrence-free survival between two groups. Univariate COX regression and stratified analyses were performed to screen and identify survival predictors for PA-TACE patients. The identified predictive markers were validated in an external cohort. RESULTS: The propensity analysis matched 116 patients in PA-TACE group to 232 in the control group. Visible protective effect of PA-TACE was shown by survival curves in matched series (log-rank P=0.009 and 0.008), with hazard ratio of being 0.599 (95% confidence interval: 0.420-0.855) and 0.623 (95% confidence interval: 0.449-0.866), respectively, for overall survival and recurrence-free survival. The identified prognostic predictors for PA-TACE included TNM stage, tumor size and number, hepatitis B infection, spleen diameter, preoperative serum α-fetoprotein, alkaline phosphatase, γ-glutamyl transpeptidase and monocyte, and three risk signatures (aspartate aminotransferase-to-alanine aminotransferase ratio, neutrophil-to-lymphocyte ratio, and systemic immune-inflammation index). CONCLUSION: The treatment effectiveness of adjuvant transcatheter arterial chemoembolization for patients with hepatocellular carcinoma after surgery was validated in this study, and the best candidates for PA-TACE were identified as well, including patients with late-stage tumor, portal hypertension, and high preoperative serum levels of α-fetoprotein, alkaline phosphatase, γ-glutamyl transpeptidase, and monocytes.

A new risk score based on twelve hepatocellular carcinoma-specific gene expression can predict the patients' prognosis.

A large panel of molecular biomarkers have been identified to predict the prognosis of hepatocellular carcinoma (HCC), yet with limited clinical application due to difficult extrapolation. We here generated a genetic risk score system comprised of 12 HCC-specific genes to better predict the prognosis of HCC patients. Four genomics profiling datasets (GSE5851, GSE28691, GSE15765 and GSE14323) were searched to seek HCC-specific genes by comparisons between cancer samples and normal liver tissues and between different subtypes of hepatic neoplasms. Univariate survival analysis screened HCC-specific genes associated with overall survival (OS) in the training dataset for next-step risk model construction. The prognostic value of the constructed HCC risk score system was then validated in the TCGA dataset. Stratified analysis indicated this scoring system showed better performance in elderly male patients with HBV infection and preoperative lower levels of creatinine, alpha-fetoprotein and platelet and higher level of albumin. Functional annotation of this risk model in high-risk patients revealed that pathways associated with cell cycle, cell migration and inflammation were significantly enriched. In summary, our constructed HCC-specific gene risk model demonstrated robustness and potentiality in predicting the prognosis of HCC patients, especially among elderly male patients with HBV infection and relatively better general conditions.

A seven-long noncoding RNA signature predicts overall survival for patients with early stage non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is the most common cancer and cause of cancer-related mortality globally. Increasing evidence suggested that the long non-coding RNAs (lncRNAs) were involved in cancer-related death. To explore the possible prognostic lncRNA biomarkers for NSCLC patients, in the present study, we conducted a comprehensive lncRNA profiling analysis based on 1902 patients from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets. In the discovery phase, we employed 682 patients from the combination of four GEO datasets (GSE30219, GSE31546, GSE33745 and GSE50081) and conducted a seven-lncRNA formula to predict overall survival (OS). Next, we validated our risk-score formula in two independent datasets, TCGA (n=994) and GSE31210 (n=226). Stratified analysis revealed that the seven-lncRNA signature was significantly associated with OS in stage I patients from both discovery and validation groups (all P<0.001). Additionally, the prognostic value of the seven-lncRNA signature was also found to be favorable in patients carrying wild-type KRAS or EGFR. Bioinformatical analysis suggested that the seven-lncRNA signature affected patients' prognosis by influencing cell cycle-related pathways. In summary, our findings revealed a seven-lncRNA signature that predicted OS of NSCLC patients, especially in those with early tumor stage and carrying wild-type KRAS or EGFR.

A three-long non-coding RNA-expression-based risk score system can better predict both overall and recurrence-free survival in patients with small hepatocellular carcinoma.

Growing evidence indicates that long non-coding RNAs (lncRNAs) may be potential biomarkers and therapeutic targets for many disease conditions, including cancer. In this study, we constructed a risk score system of three lncRNAs (LOC101927051, LINC00667 and NSUN5P2) for predicting the prognosis of small hepatocellular carcinoma (sHCC) (maximum tumor diameter ≤5 cm). The prognostic value of this sHCC risk model was confirmed in TCGA HCC samples (TNM stage I and II). Stratified survival analysis revealed that the suitable patient groups of the sHCC lncRNA-signature included HBV-infected and cirrhotic patients with better physical conditions yet lower levels of albumin and higher levels of alpha-fetoprotein preoperatively. Besides, Asian patients with no family history of HCC or history of alcohol consumption can be predicted more precisely. Molecular functional analysis indicated that PYK2 pathway was significantly enriched in the high-risk patients. Pathway enrichment analysis indicated that the two lncRNAs (LINC00667 and NSUN5P2) associated with poor prognosis were closely related to cell cycle. The nomogram based on the lncRNA-signature for RFS prediction in sHCC patients exhibited good performance in recurrence risk stratification. In conclusion, we identified a novel three-lncRNA-expression-based risk model for predicting the prognosis of sHCC.

Devascularization of the superior mesenteric vein without reconstruction during surgery for retroperitoneal liposarcoma: A case report and review of literature.

A 61-year-old female patient with chronic hepatitis B virus infection was diagnosed with liposarcoma in a community hospital. Fine needle aspiration biopsy confirmed the diagnosis of well-differentiated liposarcoma. Abdominal computed tomographic angiography (CTA) showed that the mass adhered to and constricted the main trunk and branch of the superior mesenteric vein (SMV), especially the ileocolic vein, and collateral circulation was observed during the vascular reconstruction scan. The abdominal liposarcoma was resected. Because of the collateral circulation, devascularization of the SMV was attempted, and we resected the eroded SMV. The condition of the blood vessels was evaluated 20 d after surgery using CTA, which showed that the SMV had disappeared. Significant improvements in SMV collateral circulation and the inferior mesenteric vein were observed after vascular reconstruction. The patient had an uneventful postoperative course except for transient gastroplegia. Twenty months after surgery, the patient had a recurrence of liposarcoma. She underwent tumor resection to remove the distal small intestine and right hemicolon. We learned that (1) direct devascularization of the main SMV trunk without a vein graft is possible. The presence of collateral circulation can increase the success rate of patients undergoing radical surgery and prevent the occurrence of serious postoperative complications. In addition, (2) this case demonstrated the clinical value of 3D reconstruction.

Comprehensive analysis and experimental verification of LINC01314 as a tumor suppressor in hepatoblastoma.

Hepatoblastoma (HB), as a common pediatric liver malignancy, is composed of a variety of subgroups with different clinical outcomes. Long-noncoding RNA (lncRNA) has crucial roles in cancer biology. However, the association between lncRNA and HB has not been fully investigated. In this study, we screened lncRNA expression profiles that were annotated from the GSE75271 dataset. A total of 225 differentially expressed lncRNAs (DELs) were identified based on comparison between three prognostic subgroups, and seven of them (XR_241302, XR_923061, NR_038322, XR_951687, XR_934593, NR_120317 and XR_93406) that exhibited highly predictive accuracies were selected for functional analysis. Weighted gene correlation network analysis (WGCNA) was employed to predict the biological functions of the seven DELs. The Hippo-YAP signaling pathway was predicted to be the most statistically significant predicted pathway associated with the seven DELs. Furthermore, we performed in vitro experiments to validate the biological function of one DEL, NR_120317 (LINC01314). Our results showed decreased proliferation and migration activities of HB cells overexpressing LINC01314. Moreover, mechanistic investigations revealed that LINC01314 overexpression inhibited nuclear translocation of YAP, by inducing MST1 expression and promoting phosphorylation of LATS1 and YAP, consequently downregulating the expression of cell cycle regulatory proteins (MCM7 and cyclin D1). Taken together, our findings provide evidence for LINC01314 as a potential biomarker and anti-cancer therapeutic target in patients with HB.

Long non-coding RNA KCNQ1OT1 mediates the growth of hepatocellular carcinoma by functioning as a competing endogenous RNA of miR-504.

Accumulating evidence highlights the fact that long non­coding RNAs (lncRNAs) serve as critical factors in the growth of hepatocellular carcinoma (HCC). The dysregulation of lncRNA KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) has been reported in numerous human benign diseases. However, the role of KCNQ1OT1 in human HCC remains poorly understood. In this study, we demonstrated that the expression of KCNQ1OT1 was abnormally increased in HCC tissues. The ectopic high expression of KCNQ1OT1 was associated with liver cirrhosis, a larger tumor size, an advanced TNM stage, and a worse overall survival and tumor­free survival. For the first time, to the best of our knowledge, we report that KCNQ1OT1 knockdown results in a decreased cell viability and colony formation ability, and an increased rate of apoptosis in vitro. The results from our in vivo results demonstrated that KCNQ1OT1 silencing attenuated tumor growth by impairing cell proliferation. Additionally, we found that KCNQ1OT1 exerted its effects partly by relying on the microRNA­504 (miR­504)­mediated regulation of cyclin­dependent kinase 16 (CDK16), in addition to the regulation of the glycogen synthase kinase 3ß (GSK3ß)/ß­catenin/Bcl­2 signaling pathway. The present study revealed the functions and mechanisms of action of lncRNA KCNQ1OT1 regarding its role in promoting the growth of HCC. Thus, lncRNA KCNQ1OT1 may prove to be a potential therapeutic target for human HCC.

MicroRNA-1271 functions as a metastasis and epithelial-mesenchymal transition inhibitor in human HCC by targeting the PTP4A1/c-Src axis.

MicroRNAs (miRNAs or miRs) have been shown to regulate hepatocellular carcinoma (HCC) metastasis. In the present study, we focused on the functions of miR-1271 in HCC metastasis. The downregulation of miR-1271 was found to be associated with to venous infiltration, an advanced TNM stage (III+IV stage) and a shorter survival time. Our in vitro and in vivo data demonstrated that miR-1271 prevented HCC cell migration and invasion, as well as the formation of lung metastatic clusters. In addition, miR-1271 was demonstrated to markedly inhibit the epithelial-mesenchymal transition (EMT) of HCC cells. Importantly, protein tyrosine phosphatase type IVA member 1 (PTP4A1) was identified as a direct downstream target of miR-1271 in HCC. Furthermore, we confirmed that the phosphorylation of c-Src at Tyr416 mediated by PTP4A1 was a potential anti-HCC mechanism of action of miR-1271. On the whole, our data indicate that miR-1271 inhibits HCC metastasis by targeting the PTP4A1/c-Src signaling pathway and may serve as a prospective cancer therapeutic target for HCC.