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Pancreatic ductal adenocarcinoma (PDAC) is one of most lethal cancers and is projected to be the second leading cause of cancer deaths in the United States by 2030. The lack of effective treatment and increased incidence in PDAC encourage a deeper knowledge of PDAC progression. By analyzing a long noncoding RNA (lncRNA) dataset, we found that increased LINC00941 expression led to poor outcomes in PDAC patients. Furthermore, in vitro and in vivo experiments revealed that LINC00941 promoted PDAC cancer cell growth by enhancing aerobic glycolysis. Mechanistically, LINC00941 was found to interact with mammalian STE20-like protein kinase 1 (MST1), which facilitated the protein phosphatase 2A (PP2A)-mediated dephosphorylation of MST1, resulting in Hippo pathway activation and consequently, enhanced glycolysis in PDAC. These results suggest that LINC00941 plays a key role in regulating PDAC tumorigenesis, potentially highlighting novel avenues for PDAC therapy., Graphical abstract, Increased LINC00941 in PDAC enhances the interaction between MST1 and PP2A, which facilities PP2A-mediated dephosphorylating of MST1, resulting in Hippo pathway activation and enhancing the glycolysis in the PDAC cell, consequently promoting the progression of pancreatic cancer.

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Ru Huang,1,* Kaijing Wang,2,* Lei Gao,1 Wei Gao2 1Department of Heart Failure, Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 2Department of Colorectal Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei GaoDepartment of Colorectal Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of ChinaEmail yoursgaowei@163.comLei GaoDepartment of Heart Failure, Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of ChinaEmail gldlykdx@163.comPurpose: Colorectal cancer (CRC) is the third most frequently diagnosed cancer worldwide. As a high-risk factor for CRC, ulcerative colitis (UC) has been demonstrated to lead to epithelial dysplasia, DNA damage, and eventually cancer. There are approximately 18% of patients with UC may develop CRC.Patients and methods: The gene expression profiles were retrieved from the Gene Expression Omnibus. The Database for Annotation, Visualization and Integrated Discovery was employed to conduct gene annotations. Protein-protein interaction network was constructed by the Search Tool for the Retrieval of Interacting Genes, and further analysed by the Molecular Complex Detection. The correlation between TIMP1 and prognosis was evaluated by the Gene Expression Profiling Interactive Analysis. To predict the potential functions of TIMP1, the GeneMANIA, Coremine, and FunRich were employed. After transfection with small interfering RNA targeting TIMP1, cell proliferation, migration, and apoptosis were determined by CCK-8, scratch wound, and Annexin V-FITC/PI assays, respectively.Results: TIMP1, consistently overexpressed in the initiation and progression of UC-associated CRC (ucaCRC), was identified to be a potential biomarker for the prognosis of patients with CRC. Experimental results showed knockdown of TIMP1 could increase the migration, while did not affect the proliferation and apoptosis of RKO cells. The role of TIMP1 in the malignant transformation of ucaCRC was confirmed by using the protein/gene interactions and biological process annotation and validated by analysing the transcription factors targeting TIMP1.Conclusion: TIMP1 is consistently upregulated in the pathological process of ucaCRC and can be a potential biomarker for the worse prognosis of CRC.Keywords: colitis ulcerative, colorectal neoplasms, high-throughput screening assays, prognosis

Background: Transrectal natural orifice specimen extraction (NOSE) is less invasive compare to traditional laparoscopic-assisted anterior resection (LAR). However, psychological evaluation of patients after transrectal LAR-NOSE is needed to evaluate its clinical feasibility. This study aimed to compare patient outcomes between LAR and LAR-NOSE.Methods: We studied 215 patients with colorectal cancer who underwent surgery between June 2015 and April 2018; they were randomized into two groups: LAR-NOSE (n=109) and LAR (n=106). Data on pain, anxiety, and depression were collected and compared. Pain was assessed by a visual analogue scale (VAS) and anxiety and depression by the self-rating anxiety scale (SAS), self-rating depression scale (SDS), and state-trait anxiety inventory. The overall survival and 5-year disease-free survival (DFS) rates were noted.Results: The extraction success rate in the LAR-NOSE group was 87.1% (95/109 cases). The LAR-NOSE SAS (44.21 ± 8.46) and SDS (37.29 ± 8.98) scores were significantly lower than the LAR scores (51.04 ± 9.12 and 44.65 ± 9.27, respectively; PPPConclusion: patients in the LAR-NOSE group showed better outcomes related to postoperative anxiety and depression, postoperative complications, and short-term postoperative recovery. Our results suggest transrectal NOSE as a feasible and potentially preferable method for treatment in selected patients.Registration No: SHDFYY2015-098 Date:2015.02.01

Aim: To study the impact of sleeve gastrectomy plus side-to-side jejunoileal anastomosis on weight loss and the remission of type 2 diabetes mellitus. Methods: Thirty-three 7 weeks old male Zucker diabetic fatty rats were randomized into three groups: sleeve gastrectomy plus side-to-side jejunoileal anastomosis (JI-SG group), sleeve gastrectomy (SG group), sham surgery (Control group). Results: The weight of rats in JI-SG group and SG group was significantly lower than control group at 2 weeks postoperatively, and body weight in JI-SG group was lower than SG group since 4 week postoperatively. The blood Glucose was significantly improved for both JI-SG group and SG group, and increased in Control group at 2 weeks after surgery. The serum ghrelin level of rats in JI-SG, SG group was significantly decreased, but without difference between two groups; compared with that preoperatively, the GLP-1 level of rats in JI-SG group was significantly higher at 12 weeks postoperatively; SG group and SO group had no difference in the GLP-1. The serum insulin level in rats was also decreased in JI-SG group and SG group at 6 weeks postoperatively, and plasma insulin level in JI-SG group was significantly lower than those in the SG group at 12 weeks postoperatively. Conclusions: JI-SG is superior to SG as the treatment of type 2 diabetes mellitus and weight control in obese diabetic rodents.