N6-methyladenosine modification of OIP5-AS1 promotes glycolysis, tumorigenesis, and metastasis of gastric cancer by inhibiting Trim21-mediated hnRNPA1 ubiquitination and degradation.

BACKGROUND: Opa-interacting protein 5 antisense transcript 1 (OIP5-AS1) has been demonstrated to play vital roles in development and progression of tumors such as gastric cancer (GC). However, the detailed molecular mechanism of OIP5-AS1 has not been completely elucidated. Our study aimed to investigate the role and the epigenetic regulation mechanism of OIP5-AS1 in GC. METHODS: OIP5-AS1 expression in GC tissues was detected by RT-qPCR. Loss- and gain-of-function experiments were conducted to assess the biological function of OIP5-AS1 in vitro and in vivo. The interaction of OIP5-AS1 with insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) or heterogeneous nuclear nucleoprotein A1 (hnRNPA1) was verified by bioinformatics analysis, RNA pull-down assays, and RNA immunoprecipitation assays. RESULTS: In this study, we identified that OIP5-AS1 is specifically overexpressed in GC tumor tissues and cell lines and correlated with a poor prognosis. The loss of OIP5-AS1 suppressed the proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and glycolysis of GC cells, but the ectopic expression of OIP5-AS1 had the opposite impact. Meanwhile, knockdown of OIP5-AS1 inhibited tumor growth in patient-derived xenograft models, as well as repressed tumor metastasis. Mechanistically, IGF2BP3 could bind to OIP5-AS1 by N6-methyladenosine (m6A) modification sites on OIP5-AS1, thereby stabilizing OIP5-AS1. Moreover, OIP5-AS1 prevented Trim21-mediated ubiquitination and degradation of hnRNPA1, stabilizing hnRNPA1 protein and promoting the malignant progression of GC by regulating PKM2 signaling pathway. CONCLUSIONS: In conclusion, this study highlighted that OIP5-AS1 is an oncogenic m6A-modified long non-coding RNA (lncRNA) in GC and that IGF2BP3/OIP5-AS1/hnRNPA1 axis may provide a potential diagnostic or prognostic target for GC.

Impact of combining Lenvatinib with Transarterial chemoembolization for unresectable hepatocellular carcinoma.

Objectives: To investigate the impact of combining lenvatinib with transarterial chemoembolization (TACE) for unresectable hepatocellular carcinoma (HCC). Methods: This was a retrospective observational study which reviewed the medical records of 103 unresectable HCC patients from January 2017 to June 2020 in The First Affiliated Hospital of Soochow University. It included 46 patients who received TACE plus lenvatinib and 57 patients who received TACE alone. The levels of serum indicators, clinical effect, adverse events, overall survival (OS), and progression-free survival (PFS) were compared between the two groups. Results: AFP and VEGF levels in the TACE+lenvatinib group post-treatment were significantly lower than the TACE group (P<0.05). The clinical efficacy in the TACE+lenvatinib group (69.57%) was higher than that in the TACE group (40.35%) post-treatment (P<0.05). There were significant differences in hypertension, diarrhea, and bleeding (gingiva) between the two groups (P<0.05). There were no significant differences in one or two year PFS rate or one year OS between groups (P>0.05), while the two years survival rate in the TACE+lenvatinib group was significantly higher than that in the TACE group (P<0.05). Conclusions: TACE combined with lenvatinib have a high clinical effective rate, with reduced AFP and VEGF levels, higher two year survival rate, and acceptable incidence of adverse events.

Development of o-aminobenzamide salt derivatives for improving water solubility and anti-undifferentiated gastric cancer.

Background: Gastric cancer is one of the cancers with wide incidence, difficult treatment and high mortality in the world, especially in Asia and Africa. In our previous work, a novel o-aminobenzamide analogue F8 was identified as an early preclinical candidate for treatment of undifferentiated gastric cancer (IC50 of 0.26 µM for HGC-27). However, the poor water solubility of compound F8 prevents its further progress in preclinical studies. Aim: To improve the water solubility and drug-likeness of F8 via salt formation. Method: Different acids and F8 were reacted to obtain different salt forms. Physicochemical property screening, pharmacokinetic property research, and antitumor biological activity evaluation in vitro and in vivo were used to obtain the optimal salt form with the best druggability. Results: our continuous efforts have finally confirmed F8·2HCl as the optimal salt form with maintained in vitro antitumor activity, improved water solubility and pharmacokinetic properties. Importantly, the F8·2HCl displayed superior in vivo antitumor efficacy (TGI of 70.1% in 75 mg/kg) in HGC-27 xenograft model. The further immunohistochemical analysis revealed that F8·2HCl exerts an antitumor effect through the regulation of cell cycle-related protein (CDK2 and p21), apoptosis-related protein Cleaved Caspase-3, proliferation marker Ki67, and cell adhesion molecule E-cadherin. In addition, F8·2HCl showed acceptable safety in the in vivo acute toxicity assay. Conclusion: Salting is an effective means to improve the drug-like properties of compound F8, and F8·2HCl can serve as a promising therapeutic agent against undifferentiated gastric cancer.

Diverse roles of UBE2T in cancer (Review).

As a leading cause of mortalities worldwide, cancer results from accumulation of both genetic and epigenetic alterations. Disruption of epigenetic regulation in cancer, particularly aberrant ubiquitination, has drawn increasing interest in recent years. The present study aimed to review the roles of ubiquitin­conjugating enzyme E2 T (UBE2T) and its associated pathways in the pathogenesis of pan­cancer, and the development of small­molecule modulators to regulate ubiquitination for treatment strategies. The current study comprehensively investigated the expression landscape and functional significance of UBE2T, as well as its correlation with cancer cell sensitivity to chemotherapy/radiotherapy. Multiple levels of evidence suggested that aberrant UBE2T played important roles in pan­cancer. Information was collected from 16 clinical trials on ubiquitin enzymes, and it was found that these molecules had an important role in the ubiquitin­proteasome system. Further studies are necessary to explore their feasibility and effectiveness as diagnostic and prognostic biomarkers, or as up/down­stream and therapeutic targets for cancer treatment.

Tim-3 blockade enhances the clearance of Chlamydia psittaci in the lung by promoting a cell-mediated immune response.

Chlamydia psittaci is remarkable at disrupting immunity and thus poses a great risk to the animal industry and public health. Immune inhibitory molecule upregulation and the accumulation of specialized cells play key roles in chlamydial clearance. It is clear that the T-cell immunoglobulin and mucin domain protein 3 receptor (Tim-3) can regulate effector T cells in infectious disease. However, the immunomodulatory effect of Tim-3 in C. psittaci infection remains unknown. Thus, the expression of Tim-3 in effector T cells and its immune regulatory function during C. psittaci infection were investigated. The level of Tim-3 on CD4+ and CD8+ T cells was meaningfully higher in C. psittaci-infected mice. Blockade of Tim-3 signaling by anti-Tim-3 antibody showed accelerated C. psittaci clearance and less pathological changes in the lung than isotype immunoglobulin treatment. Furthermore, treatment with anti-Tim-3 antibody greatly enhanced the levels of IFN-γ and interleukin (IL)-22/IL-17, which were correlated with an improved Th1- and Th17-mediated immune response, and decreased IL-10, which were related with a decreased Treg immune response. In conclusion, Tim-3 expression in effector T cells negatively regulates Th1 and Th17 immune responses against C. psittaci respiratory infection.

LncRNA NUTM2A-AS1 aggravates the progression of hepatocellular carcinoma by activating the miR-186-5p/KLF7-mediated Wnt/beta-catenin pathway.

Emerging evidence has uncovered that noncoding RNAs (ncRNAs) contribute to the development of hepatocellular carcinoma (HCC). Nevertheless, the functions of the majority of long ncRNAs (lncRNAs) in HCC are unknown. Here, we intend to probe the function of lncRNA NUTM2A-AS1 in the evolvement of HCC and the related mechanism. Expression levels of lncRNA NUTM2A-AS1, miR-186-5p and KLF7 mRNA in HCC tissues and adjacent non-tumor tissues were monitored. Gain- or loss-of-function assays were utilized to investigate the biological functions of lncRNA NUTM2A-AS1, miR-186-5p and KLF7 in HCC cell lines (including HCCLM3 and Huh7). Western blot was implemented for the detection of the epithelial-mesenchymal transition (EMT)-related proteins (including E-cadherin, Vimentin and Snail), KLF7, Wnt, ß-catenin, and stemness-related proteins (Nanog, OCT4, YKL40, and CD133). Furthermore, the targeted associations between lncRNA NUTM2A-AS1, miR-186-5p, and KLF7 were verified by bioinformatics analysis, dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. As a result, lncRNA NUTM2A-AS1 and KLF7 profiles were heightened in the HCC tissues versus adjacent normal tissues, while miR-186-5p had the opposite expression tendency. Up-regulation of lncRNA NUTM2A-AS1 was related to tumor size, advanced tumor stage, and lymph node metastasis of HCC patients. Functionally, overexpression of lncRNA NUTM2A-AS1 heightened HCC cells' growth, invasion, EMT, and stemness and repressed their apoptosis by activating the Wnt/ß-catenin pathway. In contrast, up-regulation of miR-186-5p or inhibition of KLF7 had reverse effects. In vivo, lncRNA NUTM2A-AS1 overexpression facilitated tumor growth and EMT, accompanied by declined miR-186-5p levels and enhanced KLF7 expression. The mechanistic studies revealed that miR-186-5p served as a common target of lncRNA NUTM2A-AS1 and KLF7. As hinted by the rescue experiments, NUTM2A-AS1 partly abated miR-186-5p-mediated anti-tumor effects in HCC cells, whereas KLF7 knockdown reversed the promotive effects of NUTM2A-AS1. LncRNA NUTM2A-AS1 accelerated the evolution of HCC by up-regulating the KLF7/Wnt/beta-catenin pathway through sponging miR-186-5p.

Analysis of Clinical Effects of Intubation and Sphincterotomy With Wire-guided Incision Knife Plus Balloon Dilatation in the Treatment of Choledocholithiasis: A Randomized Controlled Trial.

BACKGROUND: To investigate the clinical effects of intubation and sphincterotomy with wire-guided incision knife plus balloon dilatation (ISBD) in the treatment of choledocholithiasis, a randomized controlled trial was conducted. METHODS: A total of 270 patients with choledocholithiasis confirmed by computed tomography or magnetic resonance imaging from January 2016 to July 2018 in our hospital were enrolled in the research. All patients were randomly divided into 3 groups: ISBD group, endoscopic sphincterotomy (EST) group, and endoscopic sphincterotomy plus balloon dilation group, respectively. The clinical effects, complications, and inflammation indexes of the 3 groups were detected. SPSS software was used for statistics and analysis of results. RESULTS: There were no significant differences in basic characteristics of the 3 groups. Although there was no significant difference in the total stone clearance rate among the 3 groups, the first stone clearance rate and the large stone clearance rate in ISBD group were significantly higher than those in EST group. Compared with the other 2 groups, the total operation time and complications in ISBD group were significant lower. The serum levels of interleukin-6, C-reactive protein (CRP), procalcitonin (PCT), carbohydrate antigen 19-9, and carcinoembryonic antigen in ISBD group were significant lower than those in EST group, and CRP and PCT in ISBD group were markedly lower than those in endoscopic sphincterotomy plus balloon dilation group. CONCLUSIONS: ISBD treatment simplifies the operation procedure, shortens the operation time, reduces postoperative inflammation and complications, and makes ERCP stone removal simpler, safer, and more efficient for patients with common bile duct stones.

[Clinical value of activin A in early identification of moderate and severe acute pancreatitis: a prospective study].

OBJECTIVE: To explore the value of serum activin A (ACT-A) level in early identification of moderate and severe acute pancreatitis (AP). METHODS: A prospective case control study was conducted. A total of 120 patients with AP admitted to department of hepatobiliary surgery of Affiliated Nanhua Hospital of Hengyang Medical College of University of South China between October 2020 and April 2022 were recruited. According to the revised Atlanta classification, all patients were classified into mild AP group and moderate-to-severe AP group. The blood samples within 24 hours of onset were drawn, and the serum ACT-A and C-reactive protein (CRP) levels were detected by enzyme-linked immunosorbent assay (ELISA). The Ranson score and the modified CT severity index (MCTSI) were performed. Pearson correlation method was used to analyze the correlation of various parameters. The receiver operator characteristic curve (ROC curve) was plotted to analyze the predictive value of ACT-A and CRP for moderate-to-severe AP. RESULTS: A total of 120 patients with AP were enrolled, including 83 patients with mild AP and 37 patients with moderate-to-severe AP. Serum ACT-A and CRP levels within 24 hours of onset in the moderate-to-severe AP group were significantly higher than those in the mild AP group [ACT-A (ng/L): 140.4±37.7 vs. 53.9±30.5, lg CRP: 1.42±0.91 vs. 0.77±0.70, both P < 0.01], and the Ranson score and MCTSI score were also significantly higher than those in the mild AP group (Ranson score: 5.3±1.3 vs. 1.8±1.6, MCTSI score: 5.5±1.0 vs. 2.7±1.2, both P < 0.01). Correlation analysis showed that the serum ACT-A level was positively correlated with serum CRP level, Ranson score and MCTSI score (R2 value was 0.272, 0.841, 0.616, respectively, all P < 0.05). ROC curve analysis showed that the serum ACT-A, CRP and Ranson score had predictive value for moderate-to-severe AP. The area under the ROC curve (AUC) was 0.948 [95% confidence interval (95%CI) was 0.909-0.986], 0.711 (95%CI was 0.606-0.815), 0.946 (95%CI was 0.910-0.982), respectively. When serum ACT-A > 112.6 ng/L, the sensitivity and specificity of predicting moderate-to-severe AP were 78.38% and 96.39%, respectively, which was better than serum CRP with sensitivity and specificity of 72.92% and 66.27%, respectively, and the specificity was better than Ranson score (71.08%). CONCLUSIONS: ACT-A can be detected in the early stage of AP, and it is positively correlated with the disease severity, which can early identify moderate-to-severe AP.

HLA-DQB1-AS1 Promotes Cell Proliferation, Inhibits Apoptosis, and Binds with ZRANB2 Protein in Hepatocellular Carcinoma.

Major histocompatibility complex, class II, DQ beta 1 antisense RNA 1 (HLA-DQB1-AS1) conferred the susceptibility to hepatocellular carcinoma. Sustaining cell growth and resisting apoptosis are two hallmarks of hepatocellular carcinoma. The present study explored the role of HLA-DQB1-AS1 in the proliferation and apoptosis of hepatocellular carcinoma cells and investigated its downstream pathway. Colony formation assay was performed to assess cell proliferation. Cell apoptosis was assessed with the TdT-mediated dUTP nick end labeling method. HLA-DQB1-AS1 deficiency exerts antiproliferative and proapoptotic effects on hepatocellular carcinoma cells. Moreover, based on bioinformatic analysis combined with the results of RNA immunoprecipitation assay, HLA-DQB1-AS1 was revealed to bind with zinc finger RANBP2-type containing 2 (ZRANB2) protein. ZRANB2 was upregulated in hepatocellular carcinoma at a clinical and cellular level. HLA-DQB1-AS1 caused no significant effects on ZRANB2 mRNA and protein expression. ZRANB2 knockdown suppressed cell proliferation and enhanced cell apoptosis of hepatocellular carcinoma. Moreover, ZRANB2 overexpression rescued the anticancer effect of silenced HLA-DQB1-AS1 in hepatocellular carcinoma cells. In conclusion, HLA-DQB1-AS1 promotes cell proliferation and inhibits apoptosis in hepatocellular carcinoma by the interaction with ZRANB2 protein.

Long non-coding RNA FEZF1-AS1 promotes rectal cancer progression by competitively binding miR-632 with FAM83A.

The long non-coding RNA (lncRNA) forebrain embryonic zinc finger protein 1 antisense RNA1 (FEZF1-AS1) was recently identified as an oncogenic gene in several types of tumors. The biological function of FEZF1-AS1 in rectal cancer progression, however, remains unknown. In the present study, we discover that FEZF1-AS1 is significantly upregulated in rectal cancer tissues and cells. Knocking down of FEZF1-AS1 suppresses cell proliferation, migration, and invasion , and tumorigenesis . Furthermore, FEZF1-AS1 functions as a competing endogenous RNA (ceRNA) for miR-632, resulting in the suppression of family with sequence similarity 83, member A (FAM83A). Overall, our findings reveal that FEZF1-AS1/miR-632/FAM83A axis plays an oncogenic role in rectal cancer progression, suggesting that it may be a novel therapeutic target for rectal cancer.

Identification of the diagnostic genes and immune cell infiltration characteristics of gastric cancer using bioinformatics analysis and machine learning.

Background: Finding reliable diagnostic markers for gastric cancer (GC) is important. This work uses machine learning (ML) to identify GC diagnostic genes and investigate their connection with immune cell infiltration. Methods: We downloaded eight GC-related datasets from GEO, TCGA, and GTEx. GSE13911, GSE15459, GSE19826, GSE54129, and GSE79973 were used as the training set, GSE66229 as the validation set A, and TCGA & GTEx as the validation set B. First, the training set screened differentially expressed genes (DEGs), and gene ontology (GO), kyoto encyclopedia of genes and genomes (KEGG), disease Ontology (DO), and gene set enrichment analysis (GSEA) analyses were performed. Then, the candidate diagnostic genes were screened by LASSO and SVM-RFE algorithms, and receiver operating characteristic (ROC) curves evaluated the diagnostic efficacy. Then, the infiltration characteristics of immune cells in GC samples were analyzed by CIBERSORT, and correlation analysis was performed. Finally, mutation and survival analyses were performed for diagnostic genes. Results: We found 207 up-regulated genes and 349 down-regulated genes among 556 DEGs. gene ontology analysis significantly enriched 413 functional annotations, including 310 biological processes, 23 cellular components, and 80 molecular functions. Six of these biological processes are closely related to immunity. KEGG analysis significantly enriched 11 signaling pathways. 244 diseases were closely related to Ontology analysis. Multiple entries of the gene set enrichment analysis analysis were closely related to immunity. Machine learning screened eight candidate diagnostic genes and further validated them to identify ABCA8, COL4A1, FAP, LY6E, MAMDC2, and TMEM100 as diagnostic genes. Six diagnostic genes were mutated to some extent in GC. ABCA8, COL4A1, LY6E, MAMDC2, TMEM100 had prognostic value. Conclusion: We screened six diagnostic genes for gastric cancer through bioinformatic analysis and machine learning, which are intimately related to immune cell infiltration and have a definite prognostic value.

Curcumin protects radiation-induced liver damage in rats through the NF-κB signaling pathway.

BACKGROUND: Curcumin has been demonstrated to exert anti-oxidant, anti-fibrotic, anti-inflammatory, and anti-cancer activities. This study was conducted to observe the effect and inner mechanism of curcumin in rats with radiation-induced liver damage (RILD). METHODS: Thirty SD rats were classified into Control, Radiation group and Curcumin (Cur) + Radiation group (n = 10 in each group). The changes in body weight of the rats were observed on the 3rd, 7th and 14th days after the treatment with curcumin. On the 14th day post treatment, the heart blood of the rats was drawn for measurement of liver function indices including total protein (TP), alanine aminotransfetase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) as well as aspartate aminotransfetase (AST). Subsequently, the rats were euthanized and liver tissues were taken to observe liver morphological changes using hematoxylin-eosin (HE), and to analyze apoptosis condition using transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) assays. Meanwhile, the oxidative stress level in liver tissue homogenate was determined by biochemical analysis. The expression of nuclear factor kappa B (NF-κB) pathway-associated and apoptosis-associated proteins was detected using Western blot analysis, and the expression levels of inflammatory factors were measured by Enzyme-linked immunosorbent assay (ELISA). RESULTS: The reduced body weight was observed in rats of the Radiation group compared to the Control and Cur + Radiation groups on day 14. In the Radiation group, hepatic cell edema and inflammatory cell infiltration could be visible under the light microscope, and the hepatocytes presented with vacuolar degeneration. In the Cur + Radiation group, the hepatocytes swelled under the microscope, but the pathological changes were alleviated in comparison with the Radiation group. RILD rats with curcumin treatment presented with decreased ALT, AST, ALP, LDH, and maleicdialdehyde (MDA) levels, and elevated TP, superoxide dismutase (SOD), caspase activated DNase (CAD) and glutathione (GSH) levels. Apoptosis and inflammation in rats with RILD were up-regulated, and the NF-κB pathway was activated, but they were reversed after continuously intragastric administration of curcumin for 14 days. CONCLUSION: Our study highlights that curcumin treatment reduces the liver damage caused by radiation through the inhibition of the NF-κB pathway.

Melatonin Attenuates Sepsis-Induced Acute Lung Injury Through Improvement of Epithelial Sodium Channel-Mediated Alveolar Fluid Clearance Via Activation of SIRT1/SGK1/Nedd4-2 Signaling Pathway.

Acute lung injury is characterized by alveolar vascular barrier injury, and protein-rich pulmonary oedema. Alveolar fluid clearance is closely related to the prognosis of patients with acute lung injury. Melatonin has been shown to have a protective effect on multiple organ injury induced by sepsis. In this study we investigated the effect of melatonin on alveolar fluid clearance (AFC) and explored its potential mechanisms in sepsis-induced acute lung injury. The cecal ligation and puncture was adopted to establish mouse sepsis model. Morphological changes of lung tissues with the hematoxylin staining were observed. AFC and lung wet/dry weight ratio were measured to assess pulmonary edema. Inflammatory mediators in bronchoalveolar lavage fluid were analyzed via enzyme-linked immunosorbent assay. NAD+/NADH and SIRT1 activity were measured by colorimetric assay kit. The protein expressions of epithelial sodium channel (ENaC), silent information regulator1 (SIRT1), SGK1 and Nedd4-2 were immunoblotted by western blot in vivo and in vitro. The distribution of α-ENaC and SIRT1 was detected by immunofluorescence. We found that melatonin attenuated sepsis induced lung injury, improved survival rate, enhanced alveolar fluid clearance, improved SIRT1 activity, increased protein expressions of SIRT1 and ENaC, and activated SGK1/Nedd4-2 pathway. Furthermore, SIRT1 inhibitor EX527 counteracted the effects of melatonin on alveolar fluid clearance and ENaC. These results revealed that melatonin enhanced ENaC-mediated AFC via the SIRT1/SGK1/Nedd4-2 signaling pathway. Our study demonstrated that melatonin might provide a novel therapeutic strategy for sepsis-induced acute lung injury.

Clinical Value of Serum LHPP-associated miR-765 in the Prognosis of Laparoscopic or Open Hepatectomy for Hepatocellular Carcinoma.

PURPOSE: The current study aims to investigate the effect of tumor suppressor LHPP-associated microRNA (miR)-765 on the prognosis of laparoscopic hepatectomy (LH) or open hepatectomy (OH) for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A total of 160 patients with HCC were enrolled and randomly divided into the LH or OH group. According to the operation time, these patients were followed up for 12 months, and the number of deaths and the corresponding death time during the follow-up period were counted. RESULTS: The authors found that the LHPP gene levels in HCC tissues were lower than that in adjacent normal tissues, whereas miR-765 was overexpressed in HCC tissue. Overexpression of miR-765 promoted the epithelial-mesenchymal transition and proliferation and inhibited apoptosis of HCC through directly downregulating LHPP expression. Serum miR-765 expression level was significantly associated with lymph node metastasis and histologic grading. Survival analysis showed that the overall survival rate in 12 months after the operation was significantly lower in the OH-high miR-765 group (P<0.05). CONCLUSION: For patients with a low miR-765 level, both LH and OH are available, otherwise, LH is more recommended.

LncRNA OIP5-AS1 facilitates gastric cancer cell growth by targeting the miR-422a/ANO1 axis.

OPA-interacting protein 5 antisense transcript 1 (OIP5-AS1) plays an important regulatory role in various types of cancers. However, the functional role and regulatory mechanisms of OIP5-AS1 in gastric cancer (GC) remain largely unknown. In this study, we found that the expression of OIP5-AS1 was increased in GC tissues compared with that in adjacent non-cancerous tissues, which was significantly associated with shorter overall survival time of patients. In addition, OIP5-AS1 expression was also increased in GC cell lines including NCI-N87, MKN-45, BGC-823 and SGC-7901, when compared with that in normal gastric epithelial cell line GES-1. Knockdown of OIP5-AS1 markedly suppressed the proliferation and colony formation activities of GC cells, induced G0/G1 arrest and apoptosis of GC cells in vitro, and restrained tumor growth in vivo. Mechanistically, OIP5-AS1 functions as an oncogenic competing endogenous RNA by binding to and sequestering miR-422a to elevate the expression of anoctamin-1. Our study first demonstrated that OIP5-AS1 is a critical and powerful regulator of GC pathogenesis and may represent a novel candidate target for GC therapy.

Association of the invasiveness of colon cancer with the expression of C/EBPα.

The present study aimed to investigate the association of the invasiveness of colon cancer (CC) with the expression of CCAAT/enhancer binding protein α (C/EBPα). Immunohistochemistry was performed to determine the expression of C/EBPα in the cancer and adjacent tissue samples from 48 patients with CC. A pCDGFP-C/EBPα eukaryotic expression vector was constructed, and a wound-healing assay was performed to observe the effect of transfection on the migration of SW480 cells. In addition, the expression levels of tumor invasion-associated proteins, including Kruppel-like factor 5 (KLF5), matrix metallopeptidase (MMP)-2, MMP-9, and E-cadherin (ECD) were detected subsequent to transfection. Immunohistochemistry analysis demonstrated that the rate of low C/EBPα expression in normal tissue was 6.25%, whereas the rate in CC tissues was 68.75%; this difference was statistically significant (P<0.05). The patients with lower C/EBPα expression exhibited statistically larger tumor diameters, more advanced tumor-node-metastasis (TMN) stages and a greater likelihood of lymph node metastasis. The overexpression of C/EBPα significantly reduced the mobility of SW480 cells, and the expression of KLF5, MMP-2 and MMP-9 was reduced, whereas the expression of ECD was increased. In conclusion, C/EBPα was downregulated in CC tissue samples, and associated with the TMN stage and metastasis of CC; in addition, the overexpression of C/EBPα significantly reduced the invasiveness of CC cells. This may be significant for the diagnosis and treatment of CC in the future.

Inhibition of hsa_circ_0001313 (circCCDC66) induction enhances the radio-sensitivity of colon cancer cells via tumor suppressor miR-338-3p: Effects of cicr_0001313 on colon cancer radio-sensitivity.

Circular RNA_0001313 (circ_0001313), also known as circCCDC66, is a novel circRNA that recently found to be upregulated in colon cancer tissues and promote colon cancer progression. However, the role of circ_0001313 in regulating radio-sensitivity of colon cancer and its molecular mechanism remain undetermined. Here we found circ_0001313 was significantly upregulated and miR-338-3p was downregulated in radio-resistant colon cancer tissues compared to radio-sensitive tissues. Radiation treatment in colon cells triggered a remarkable upregulation of circ_0001313 and a downregulation of miR-338-3p. Knockdown of circ_0001313 reduced cell viability, colony formation rate and increased caspase-3 activity in colon cancer cells under irradiation. Moreover, circ_0001313 act as a sponge for miR-338-3p in colon cancer cells. Furthermore, miR-338-3p could reverse the effects of circ_0001313 knockdown on cell viability, colony formation, and caspase-3 activity. These findings revealed that knockdown of circ_0001313 could induce radio-sensitivity of colon cancer cells by negatively regulating miR-338-3p.

Application of a clamp method combined with bipolar coagulation for anatomical hepatectomy in the treatment of hepatic carcinoma.

PURPOSE: This study investigated the effectiveness of a clamp method combined with bipolar coagulation for anatomical hepatectomy in the treatment of hepatocellular carcinoma (HCC). METHODS: In this prospective case-control study, three liver dissection methods were used: clamping combined with bipolar electric coagulation (group A), CUSA (Cavitron ultrasonic surgical aspirator) (group B), and ultrasonic knife (group C). Intraoperative blood loss, intraoperative blood transfusion volume, operation time, postoperative complications, aspartate aminotransferase (AST) levels, drainage volume and exhaust time, and length of postoperative hospital stay were compared among the three groups. RESULTS: Patients in group A had shorter operation times than those in group B (p<0.05), but more intraoperative blood loss. Patients in group A had shorter operations times than those in group B (p<0.05) and less intraoperative blood lost compared with group C. No statistically significant differences were found for postoperative exhaust time and length of postoperative hospital stay among groups (p>0.05). CONCLUSION: The clamps method combined with bipolar electric coagulation for liver dissection requires no special equipment and has effects similar to CUSA and ultrasonic knife dissection. Therefore, this technique is worth promoting as a common liver dissection method for anatomical hepatectomy in the treatment of primary HCC.

The prognostic significance of bromodomain PHD-finger transcription factor in colorectal carcinoma and association with vimentin and E-cadherin.

PURPOSE: Bromodomain PHD-finger transcription factor (BPTF) is a chromatin-mediated regulation of transcription factor, playing an important role in embryogenesis and differentiation. Epithelial-mesenchymal transition (EMT) has a pivotal role in colorectal cancer (CRC) progression, sharing the similar characteristic with BPTF. Therefore, the aim of this study was to examine the expression and clinical value of BPTF and the correlation with EMT markers in patients with CRC. METHODS: Real-time PCR and Western blot were performed to evaluate the mRNA and protein expression levels of BPTF in 20 pairs of fresh-frozen CRC and non-tumor adjacent tissues (NATs). The expressions of BPTF, vimentin and E-cadherin were examined by immunohistochemical staining in 105 cases of paraffin-embedded primary CRC specimens. In addition, the clinicopathological significance and the prognostic value of BPTF, vimentin and E-cadherin expression were further determined. Then, the correlation of BPTF with vimentin and E-cadherin was also explored. RESULTS: BPTF mRNA and protein expression were significantly overexpressed in CRC tissues when compared with paired NATs (P < 0.01). The expression levels of BPTF and vimentin in CRC paraffin-embedded specimens were significantly higher than the expression in NATs (P < 0.01), while the expressions of E-cadherin in tumors were obviously lower than in NATs (P < 0.01). Tumors with high expression of BPTF and vimentin, as well as low expression of E-cadherin, were significantly correlated with various adverse clinicopathological factors (P < 0.05). The CRC patients with a high BPTF or vimentin expression had shorter overall survival than those with lower expression (P < 0.05). Furthermore, univariate analysis and multivariate analysis showed that high BPTF expression was an independent prognostic factor for patients with CRC. The last and more interesting Spearman rank correlation analysis and microscopic observation found that the expression of BPTF obviously correlated with the expression of EMT markers vimentin and E-cadherin. CONCLUSION: Our results strongly suggested that the high BPTF expression was significantly correlated with tumor progression and may be a potent prognostic marker of CRC. Moreover, BPTF expression was significantly associated with EMT markers vimentin and E-cadherin.

BPTF Associated with EMT Indicates Negative Prognosis in Patients with Hepatocellular Carcinoma.

BACKGROUND/AIMS: Epithelial-mesenchymal transition (EMT) plays an important role in hepatocellular carcinoma (HCC) dissemination. Bromodomain PHD-finger transcription factor (BPTF) could regulate embrogenesis and stem cell differentiation, and it may be involved in tumor progression and EMT. In this study, we aimed to determine BPTF, E-cadherin and vimentin expression in tumor tissues and the clinical significance in relation to HCC. METHODS: The BPTF, vimentin and E-cadherin expression of 106 HCC tissue samples was examined by immunohistochemical staining. RESULTS: BPTF and vimentin showed high expression and E-cadherin showed low expression in HCC. BPTF is associated with the tumor number, vascular invasion, Edmondson-Steiner grade, TNM stage and recurrence (P < 0.05). Vimentin is positively correlated with tumor size, tumor number, vascular invasion, Edmondson-Steiner grade, TNM stage and recurrence (P < 0.05). E-cadherin is negatively correlated with tumor number, Edmondson-Steiner grade, TNM stage and recurrence (P < 0.05). Survival analysis has shown that high expression of BPTF and vimentin indicates poorer overall and disease-free survival (P < 0.05). Multivariate analysis shows that BPTF is an independent marker for survival prediction (P = 0.015). Additionally, high BPTF expression is correlated with high vimentin expression and low E-cadherin expression (P < 0.05). CONCLUSION: High BPTF expression may be an independent marker for survival prediction in HCC patients and is probably involved in EMT.