The long noncoding RNA (lncRNA) H19 has been recently characterized as an oncogenic lncRNA in some tumors. However, the role of H19 in pancreatic ductal adenocarcinoma (PDAC) remains unclear. In this study, we found that not only the levels of H19 was overexpressed in PDAC compared with adjacent normal tissues, but also H19 expression was upregulated remarkably in primary tumors which subsequently metastasized, compared to those did not metastasis. Subsequently, the efficacy of knockdown of H19 by H19-small interfering RNA (siRNA) was evaluated in vitro, and we found that downregulation of H19 impaired PDAC cell invasion and migration. We further demonstrated that H19 promoted PDAC cell invasion and migration at least partially by increasing HMGA2-mediated epithelial-mesenchymal transition (EMT) through antagonizing let-7. This study suggests an important role of H19 in regulating metastasis of PDAC and provides some clues for elucidating the lncRNA-miRNA functional network in cancer.

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BackgroundmicroRNAs (miRNAs) are a class of small non-coding RNAs that play important roles in carcinogenesis. In the present study, we investigated the effect of miR-212 on pancreatic ductal adenocarcinoma (PDAC) and its target protein.MethodsQuantitative real-time PCR(qRT-PCR) was performed to detect the expression of miR-212 in PDAC tissues and pancreatic cancer cell lines. miR-212 mimic, miR-212 inhibitor and negative control were transfected into pancreatic cancer cells and the effect of miR-212 up-regulation and down-regulation on the proliferation, migration and invasion of cells were investigated. Furthermore, the mRNA and protein levels of Patched-1(PTCH1) were measured. Meanwhile, luciferase assays were performed to validate PTCH1 as miR-212 target in PDAC.ResultsmiR-212 was up-regulated in PDAC tissues and cells.Using both gain-of function and loss-of function experiments, a pro-oncogenic function of miR-212 was demonstrated in PDAC. Moreover, up-regulated of PTCH1 could attenuate the effect induced by miR-212.ConclusionThese data suggest that miR-212 could facilitate PDAC progression and metastasis through targeting PTCH1, implicating a novel mechanism for the progression of PDAC.

BackgroundThe dysregulation of oncogenes and tumor suppressor genes plays an important role in many cancers, including hepatocellular carcinoma (HCC), which is one of the most common cancers in the world. In a previous microarray experiment, we found that DLGAP5 is overexpressed in HCCs. However, whether the up-regulation of DLGAP5 contributes to hepatocarcinogenesis remains unclear. Methodology/Principal FindingsIn this study, we showed that DLGAP5 was significantly up-regulated in 76.4% (168 of 220) of the analyzed HCC specimens when compared with adjacent liver tissue. DLGAP5 overexpression was evident in 25% (22 of 88) of the HCC specimens without AFP expression, suggesting that DLGAP5 may be a novel biomarker for HCC pathogenesis. The silencing of DLGAP5 gene expression by RNA interference significantly suppressed cell growth, migration and colony formation in vitro. The expression level of DLGAP5 was also found to be related to the methylation level of its promoter in the HCC specimens. Conclusions/SignificanceTaken together, these data suggest that the expression of DLGAP5 is regulated by methylation and that the up-regulation of DLGAP5 contributes to HCC tumorigenesis by promoting cell proliferation.

SUMOylation is a dynamic process which can be reversed by a family of sentrin/SUMO-specific protease (SENPs). Recently, SENP1, a member of SENPs family was shown to have a pro-oncogenic role in many types of cancer. Here, we showed that SENP1 was upregulated in pancreatic ductal adenocarcinoma (PDAC) tissues compared with adjacent normal tissues. Moreover, clinical data showed that SENP1 was positively associated with lymph node metastasis and TNM stage. Furthermore, knockdown of SENP1 by SENP1-siRNA inhibited pancreatic cancer cell proliferation, migration, and invasion, suggesting that SENP1 played an important role in PDAC progression and metastasis. Mechanistically, silencing of SENP1 results in downregulation of MMP-9, which is pivotal for PDAC cell growth and migration. Taken together, these results suggest that SENP1 may serve as a potential novel diagnostic and therapeutic target of PDAC.

Pancreatic cancer is highly prevalent and exhibits a high incidence and mortality rate. Hypoxia contributes to tumorigenesis and the progression of pancreatic cancer. To the best of our knowledge, the role of microRNA (miR)-519 has not been investigated in hypoxia-induced pancreatic cancer progression. The purpose of the present study was to elucidate the mechanism underlying miR-519-mediated regulation of pancreatic cancer progression. Reverse transcription-quantitative PCR and western blotting were performed to investigate miR-519 and programmed death ligand 1 (PD-L1) mRNA and protein levels, respectively. Additionally, a Transwell assay was performed to examine the invasiveness of PANC-1 and SW1990 cells. Cells were subsequently stained with Annexin V to determine the apoptotic rate of cells. Furthermore, bioinformatics analysis and a dual-luciferase reporter assay were performed to confirm the direct association between miR-519 and PD-L1, and a xenograft experiment was conducted to test the role of miR-519 in vivo. The results revealed that the expression levels of miR-519 in pancreatic cancer cells were reduced following hypoxia treatment. Furthermore, transfection with miR-519 mimics inhibited PANC-1 and SW1990 cell invasiveness, and induced apoptosis under hypoxic conditions. PD-L1 was also identified as a downstream target of miR-519, and rescued the miR-519 mimic-attenuated tumorigenesis of pancreatic cancer cells under hypoxic conditions. Additionally, treatment with miR-519 mimics significantly suppressed the tumor growth of PANC-1 cells. The results of the present study indicated a novel mechanism of miR-519-mediated tumorigenesis in pancreatic cancer cells under hypoxic conditions. The conclusions may be crucial for the improvement of future pancreatic cancer treatment.

Objective To analyse potential risk factors for postoperative pancreatic fistula (POPF). Methods A retrospective study on risk factors for POPF was conducted in patients undergoing laparoscopic pancreatoduodenectomy. Basic characteristics, and preoperative, intraoperative and postoperative patient data were collected and analysed. Results A total of 268 patients were enrolled in this study, including 54 patients with POPF following surgery (POPF incidence, 20.15%). Univariate analysis indicated that patient’s age, body mass index (BMI), preoperative bilirubin level, pancreas texture, and drainage fluid amylase level on day 1 following surgery were associated with POPF. Multiple logistic regression analysis indicated that preoperative bilirubin level ≥170 µmol/l, soft pancreas texture, BMI ≥25, and age ≥65 years were independent risk factors associated with POPF. Conclusions For patients with preoperative bilirubin level ≥170 µmol/l, soft pancreas texture, BMI ≥25 and age ≥65 years, clinically relevant measures should be taken as early as possible for the prophylaxis of POPF.

Background: This retrospective study aimed to present our surgical experience in patients with benign tumour or trauma in spleen who underwent laparoscopic partial splenectomy (LPS) and to compare the results with those of patients who underwent an open partial splenectomy (OPS). Methods: We analysed the medical data of patients who underwent LPS or OPS between January 2010 and January 2020. Results: In total, 41 patients were enrolled. Nine patients underwent open surgery, 32 patients underwent laparoscopic surgery. The proportion of patients with tumours in the upper pole in LPS group was more than patients in OPS group. No difference was observed in estimated blood loss, allogeneic transfusion, postoperative stay, pathology and complications between LPS and OPS groups. The operation time in the LPS group (137.5 AE 30.8 min) was longer than that in the OPS group (88.3 AE 30.1 min) for patients with splenic traumatic rupture (P = 0.019). Conclusions: LPS is an effective and safe spleen-preserving surgery as OPS. The advantages are small trauma, light pain and quick recovery. It is suitable for patients with benign tumours or trauma confined to one side of the spleen.