CircPTPRA promotes the progression of pancreatic ductal adenocarcinoma via the miR-140-5p/LMNB1 axis.

BACKGROUND: Growing evidences suggest that circular RNAs (circRNAs) are important factors in cancer progression. Nevertheless, the role of circRNAs in the progression of pancreatic ductal adenocarcinoma (PDAC) remains unclear. METHODS: CircPTPRA was identified based on our previous circRNA array data analysis. Wound healing, transwell, and EdU assays were performed to investigate the effect of circPTPRA on the migration, invasion, and proliferation of PDAC cells in vitro. RNA pull-down, fluorescence in situ hybridization (FISH), RNA immunoprecipitation (RIP), and dual-luciferase reporter assays were conducted to verify the binding of circPTPRA with miR-140-5p. Subcutaneous xenograft model was constructed for in vivo experiment. RESULTS: CircPTPRA was significantly upregulated in PDAC tissues and cells compared to normal controls. Moreover, circPTPRA overexpression was positively correlated with lymph node invasion and worse prognosis in PDAC patients. In addition, overexpression of circPTPRA promoted PDAC migration, invasion, proliferation, and epithelial-mesenchymal transition (EMT) in vitro and in vivo. Mechanistically, circPTPRA upregulates LaminB1 (LMNB1) expression by sponging miR-140-5p and ultimately promotes the progression of PDAC. CONCLUSIONS: This study revealed that circPTPRA plays an important role in the progression of PDAC by sponging miR-140-5p. It can be explored as a potential prognostic marker and therapeutic target for PDAC.

The safety and feasibility of laparoscopic right posterior sectionectomy vs. open approach: A systematic review and meta-analysis.

Background: Laparoscopic right posterior sectionectomy (LRPS) is one of the most technically challenging and potentially hazardous procedures in laparoscopic liver resection. Although some available literature works demonstrated the safety and feasibility of LRPS, these data are limited to reports from a single institution and a small sample size without support from evidence-based medicine. So, we performed a meta-analysis to assess further the safety and feasibility of LRPS by comparing it with open right posterior sectionectomy (ORPS). Methods: MEDLINE, Embase, and Cochrane Library were systematically searched for eligible studies comparing LRPS and open approaches. Random and fixed-effects models were used to calculate outcome measures. Results: Four studies involving a total of 541 patients were identified for inclusion: 250 in the LRPS group and 291 in the ORPS group. The postoperative complication and margin were not statistically different between the two groups (OR: 0.49, 95% CI: 0.18 to 1.35, P = 0.17) (MD: 0.05, 95% CI: -0.47 to 0.57, P = 0.86), respectively. LRPS had a significantly longer operative time and shorter hospital stay (MD: 140.32, 95% CI: 16.73 to 263.91, P = 0.03) (MD: -1.64, 95% CI: -2.56 to -0.72, P = 0.0005) respectively. Conclusion: Data from currently available literature suggest that LRPS performed by an experienced surgeon is a safe and feasible procedure in selected patients and is associated with a reduction in the hospital stay.

Right hemihepatectomy combined with ligation of the common hepatic artery and gastroduodenal artery for the treatment of intrahepatic HHT: A case report.

Hereditary haemorrhagic telangiectasia (HHT) is a rare disease that lacks effective treatment. Here, the authors report the case of a 30-year-old woman presenting with abdominal pain accompanied by severe malnutrition. After a definite diagnosis of HHT involvement in the liver, liver transplantation was the first-choice treatment according to the guidelines of HHT. However, the patient firmly refused liver transplantation. Finally, a new type of surgery, right hemihepatectomy combined with ligation of the common hepatic artery and gastroduodenal artery, was performed based on careful study of the case and with the maximum benefit of the patient in mind. Although the patient developed transient liver dysfunction after surgery, she eventually recovered well and continued to be followed up. As far as we know, this is the first report of this kind of surgery for the treatment of intrahepatic HHT.

Effect of infrahepatic inferior vena cava partial clamping on central venous pressure and intraoperative blood loss during laparoscopic hepatectomy.

BACKGROUND: Infrahepatic inferior vena cava (IVC) clamping is considered to be an effective method to reduce central venous pressure (CVP) and intraoperative bleeding in liver resection. However, its efficacy and safety during laparoscopic hepatectomy (LH) remain unclear. We perform this retrospective study to evaluate its efficacy and safety during LH. METHODS: Consecutive patients scheduled for LH from September 2014 to August 2019 were retrospectively reviewed. The intraoperative parameters and postoperative outcomes were analyzed. RESULTS: All patients in the infrahepatic IVC clamping group were able to tolerate partial clamping of IVC. The CVP was significantly decreased after infrahepatic IVC clamping without hemodynamic instability (8.7 ± 1.4 cmH2O vs. 2.1 ± 1.3 cmH2O, P = 0.000). Infrahepatic IVC clamping did not significantly reduce total blood loss (287.3 ± 112.5 mL vs. 301.4 ± 127.6 mL, P = 0.133) and blood loss during parenchymal transection (273.2 ± 107.9 mL vs. 296.5 ± 118.1 mL, P = 0.618) compared with the non-clamping group. In subgroup analysis, total blood loss and blood loss during parenchymal transection were significantly reduced in patients with moderate to severe cirrhosis in the clamping group (363.6 ± 71.2 mL vs. 473.4 ± 95.6 mL, P = 0.021), (358.7 ± 70.9 mL vs. 466.9 ± 94.5 mL, P = 0.016), respectively. The complications and hospital stay were comparable. CONCLUSIONS: In conclusion, these data suggest that infrahepatic IVC clamping may be safe and effective.

The reasonable drainage option after laparoscopic common bile duct exploration for the treatment of choledocholithiasis.

OBJECTIVE: To obtain a reasonable drainage after laparoscopic common bile duct exploration (LCBDE) for the treatment of choledocholithiasis. METHODS: Data of 350 consecutive patients who underwent LCBDE in our hospital from January 2014 to December 2016 were retrospectively reviewed. All the patients were divided into three groups according to different drainage types after LCBDE, including T-tube group with 116 cases, primary closure (PC) group with 114 cases and stent insertion group with 120 cases. Operative parameters and outcomes were compared. RESULTS: The operative time was no significant difference between the T-tube group (106.71 ± 5.19 min), PC group (105.46 ± 5.77 min) and stent insertion group (106.88 ± 5.91 min) (F = 2.175, P = 0.115). The postoperative hospital stay was significantly shorter in the stent insertion group (5.62 ± 0.70 d) than in the T-tube group (7.79 ± 0.85 d) and PC group (7.60 ± 0.80 d) (F = 279.649, P = 0.000). The hospitalization cost was significantly less in the stent insertion group (19,432.78 ± 661.74 yuan) than in the T-tube group (22,059.90 ± 697.98 yuan) and PC group (21,927.20 ± 772.02 yuan) (F = 512.492, P = 0.000). The incidence of postoperative biliary-specific complications was 2.59% (3/116 cases) in the T-tube group, 2.63% (3/114 cases) in the PC group, and 0% (0/120 cases) in the stent insertion group, but this difference was not statistically significant (χ2 = 3.177, P = 0.204). The return to normal levels of postoperative liver function tests (LFTs) was significantly faster in the stent insertion group and T-tube group than in the PC group (P < 0.05). The number of 314 patients were followed up for a median time of 20 months (range from 1-48 months), and no biliary stricture, cholangitis or stone recurrence occurred in these patients during that time. CONCLUSIONS: Stent insertion shows better results when compared with T-tube drainage and primary duct closure in terms of postoperative hospital stay and hospitalization cost. It is the prior option for the choledochotomy closure after LCBDE in suitable patients.

H2AX facilitates classical non-homologous end joining at the expense of limited nucleotide loss at repair junctions.

Phosphorylated histone H2AX, termed 'γH2AX', mediates the chromatin response to DNA double strand breaks (DSBs) in mammalian cells. H2AX deficiency increases the numbers of unrepaired DSBs and translocations, which are partly associated with defects in non-homologous end joining (NHEJ) and contributing to genomic instability in cancer. However, the role of γH2AX in NHEJ of general DSBs has yet to be clearly defined. Here, we showed that despite little effect on overall NHEJ efficiency, H2AX deficiency causes a surprising bias towards accurate NHEJ and shorter deletions in NHEJ products. By analyzing CRISPR/Cas9-induced NHEJ and by using a new reporter for mutagenic NHEJ, we found that γH2AX, along with its interacting protein MDC1, is required for efficient classical NHEJ (C-NHEJ) but with short deletions and insertions. Epistasis analysis revealed that ataxia telangiectasia mutated (ATM) and the chromatin remodeling complex Tip60/TRRAP/P400 are essential for this H2AX function. Taken together, these data suggest that a subset of DSBs may require γH2AX-mediated short-range nucleosome repositioning around the breaks to facilitate C-NHEJ with loss of a few extra nucleotides at NHEJ junctions. This may prevent outcomes such as non-repair and translocations, which are generally more destabilizing to genomes than short deletions and insertions from local NHEJ.

Coexpression of HMGA2 and Oct4 predicts an unfavorable prognosis in human gastric cancer.

High mobility group protein A2 (HMGA2) and octamer-binding transcription factor 4 (Oct4) are transcription factors that play major roles in the acquisition of cancer stemness phenotypes and tumorigenicity of malignant neoplasms. The aim of this study was to analyze the association between HMGA2 and Oct4 expression and various clinicopathologic features in gastric cancer patients including invasion, metastasis, and clinical prognosis, in addition to overall survival. Immunohistochemistry was performed to explore the expression of HMGA2 and Oct4 in 158 gastric cancer and surrounding non-tumor tissues. Moreover, HMGA2 and Oct4 mRNA and protein levels were also detected by qRT-PCR and Western blotting, respectively, in 86 clinical tissue specimens and various gastric epithelial cell lines (GES-1, SGC7901, MKN45, and MKN27). Finally, associations between HMGA2 and Oct4 expression and clinicopathological features were analyzed by Pearson correlation coefficient. Survival analysis was performed by univariate and multivariate analyses. Taken together, we found that HMGA2 and Oct4 expression was significantly higher in gastric cancer tissues compared with non-cancerous tissues (P < 0.01), and HMGA2 and Oct4 protein levels were significantly higher in poorly differentiated gastric cancer cell lines (MKN45), moderately differentiated cell lines (SGC7901), and well-differentiated cell lines (MKN28) compared with human immortalized gastric epithelial cell lines (GES-1) (P < 0.01). Elevated HMGA2 and Oct4 levels were significantly associated with poor clinical prognosis (P < 0.05). Further conclusion showed that coexpression of HMGA2 and Oct4 in gastric cancer correlated with tumor invasion, metastasis, and clinical prognosis and predicted an unfavorable clinical outcome. These transcription factors may represent useful biomarkers to identify patients at high risk of postoperative recurrence.

Aberrant expression of the autocrine motility factor receptor correlates with poor prognosis and promotes metastasis in gastric carcinoma.

AMFR, autocrine motility factor receptor, also called gp78, is a cell surface cytokine receptor which has a dual role as an E3 ubiquitin ligase in endoplasmic reticulum-associated degradation. AMFR expression is associated with tumor malignancy. We here investigated the clinical significance of AMFR and its role in metastasis and prognosis in gastric cancer. Expression of AMFR, E-cadherin and N-cadherin in cancer tissues and matched adjacent normal tissues from 122 gastric cancer (GC) patients undergoing surgical resection was assessed by immunohistochemistry. Levels of these molecules in 17 cases selected randomly were also analysed by Western blotting. AMFR expression was significantly increased in gastric cancer tissues, and associated with invasion depth and lymph node metastasis. Kaplan-Meier analysis showed AMFR expression correlated with poor overall survival and an increased risk of recurrence in the GC cases. Cox regression analysis suggested AMFR to be an independent predictor for overall and recurrence-free survival. E-cadherin expression was decreased in gastric cancer tissues; conversely, N-cadherin was increased. Expression of AMFR negatively correlated with E-cadherin expression, whereas N-cadherin expression showed a significant positive correlation with AMFR expression. AMFR might be involved in the regulation of epithelial-mesenchymal transition, with aberrant expression correlating with a poor prognosis and promoting invasion and metastasis in GCs.

si-DNMT1 restore tumor suppressor genes expression through the reversal of DNA hypermethylation in cholangiocarcinoma.

OBJECTIVE: The aim of our study was to evaluate the effect of shorthairpin RNA plasmid vector knockdown of human DNA methyltransferase 1 on proliferation and the methylation status and expression of tumor suppressor genes in hilar cholangiocarcinoma. METHODS: The hilar cholangiocarcinoma cell line QBC939 was utilized for this study. QBC939 cells were transfected with a shorthairpin RNA plasmid vector targeting human DNA methyltransferase 1. Control and human DNA methyltransferase 1 shorthairpin RNA plasmid vector-transfected cells were collected at different time points, and the expression levels of human DNA methyltransferase 1 and tumor suppressor genes (cyclin-dependent kinase inhibitor 2B, cyclin-dependent kinase inhibitor 2A, RAS association domain family 1, and cadherin-1) were detected by reverse transcription-polymerase chain reaction. Furthermore, interfering efficiency was confirmed by Western blotting. The methylation status of tumor suppressor genes was detected using methylation-specific polymerase chain reaction. Furthermore, the effect of human DNA methyltransferase 1 knockdown on proliferation was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. RESULTS: Targeted gene knockout of human DNA methyltransferase 1 restored the expression levels of tumor suppressor genes cyclin-dependent kinase inhibitor 2B, cyclin-dependent kinase inhibitor 2A, RAS association domain family 1, and cadherin-1, indicating that the silencing of these tumor suppressor genes is associated with promoter hypermethylation. In addition, knockdown of human DNA methyltransferase 1 expression significantly inhibited the proliferation of QBC939 cells. CONCLUSIONS: Targeted knockdown of human DNA methyltransferase 1 expression restores the expression levels of tumor suppressor genes, thus inhibiting the proliferation of QBC939 cells. These results may provide insight for the development of novel therapies for cholangiocarcinoma.

Expression and role of grainyhead-like 2 in gastric cancer.

The aim of this study was to evaluate the expression and role of Grhl2 in gastric cancer. Immunohistochemistry was performed to explore the expression of Grhl2 in gastric cancer and surrounding non-tumor tissues. Moreover, the mRNA and protein expression level of Grhl2 in human immortalized gastric epithelial cell line GES-1 and four gastric cancer cell lines (MGC803, SGC7901, MKN45, HGC27) were detected by qRT-PCR and Western blotting, respectively. To further investigate the role of Grhl2 in gastric cancer as well as the potential mechanisms, SGC7901 cells were transfected with lentiviral constructs expressing Grhl2 or empty vector, and then proliferation and apoptosis of SGC7901 cells were evaluated by MTT assay and flow cytometry, respectively. Finally, the protein expression level of c-Myc and Bcl-2 was detected by Western blotting. Both mRNA and protein expression level of Grhl2 were significantly downregulated in gastric cancer. Exogenous Grhl2 transduced into SGC7901 cells significantly inhibited the proliferation and promoted apoptosis. Meanwhile, over-expression of Grhl2 decreased c-Myc and Bcl-2 protein expression level. Taken together, our results demonstrated that Grhl2 downregulated in gastric cancer and may function as a tumor suppressor and play an important role in the development and progression of gastric cancer. These results may provide a new clue for treatment for gastric cancer.