Overexpression of Rab11-FIP2 in colorectal cancer cells promotes tumor migration and angiogenesis through increasing secretion of PAI-1

Abstract Background Rab11 family-interacting protein 2 (Rab11-FIP2) can interact with MYO5B and plays an important role in regulating plasma membrane recycling. However, little is known about the clinical significance of DUSP2 in colorectal cancer (CRC). Methods In this study, we investigated Rab11-FIP2 expression by immunohistochemistry in 125 patients with colorectal cancer. Conditioned media containing all secreted factors was harvested. Chemokine secretion and expression were analyzed by Chemi-array. Results We found that the expression level of Rab11-FIP2 was significantly increased in colorectal cancer tissues and high expression of Rab11-FIP2 was closely correlated with nodal metastasis in colorectal cancer patients. Rab11-FIP2 overexpression promoted colorectal cancer metastasis in vitro and in vivo. Finally, we demonstrated that Rab11-FIP2 overexpression may contribute to increased secretion of PAI-1 in human colorectal cancer cells. Conclusions Our findings reveal a novel mechanism underlying the role of Rab11-FIP2 in colorectal cancer dissemination, suggesting that targeting Rab11-FIP2 might be a promising therapeutic strategy for CRC

MOESM5 of Overexpression of Rab11-FIP2 in colorectal cancer cells promotes tumor migration and angiogenesis through increasing secretion of PAI-1

Additional file 5: Figure S5. HUVECs were seeded on a layer of polymerized Matrigel. Cells were treated with culture media of 116/FIP2 cells with or without PAI-1 neutralizing antibody

MOESM3 of Overexpression of Rab11-FIP2 in colorectal cancer cells promotes tumor migration and angiogenesis through increasing secretion of PAI-1

Additional file 3: Figure S3. RT-PCR analysis was performed for mRNA levels of PAI-1 and GADPH (loading control) in 15/FIP2 and 116/FIP2 cells

MOESM1 of Overexpression of Rab11-FIP2 in colorectal cancer cells promotes tumor migration and angiogenesis through increasing secretion of PAI-1

Additional file 1: Figure S1. The expression of Rab11-FIP2 in 15/FIP2 and 116/FIP2 cells was confirmed by Western Blot

MOESM2 of Overexpression of Rab11-FIP2 in colorectal cancer cells promotes tumor migration and angiogenesis through increasing secretion of PAI-1

Additional file 2: Figure S2. Overexpression of Rab11-FIP2 promoted lung metastasis in HCT116-luc cells. Right panel: Representative BLI (Bioluminescence Imaging) images of mice with lung metastasis. HCT116-luc, (colorectal cancer cells expressing luciferase) were preserved in our laboratory and maintained in DMEM with 10% FBS. We established 116/FIP2-Luc cells which stably overexpressing Rab11-FIP2. 116/FIP2-Luc cells and Control cells (1 × 106) were injected into the tail veins of mice. Eight weeks later, the mice were imaged using IVES CCD imaging system. The bioluminescent signal intensity in the region of interest was quantified as total light emission using Living Image Software (Caliper Lifesciences)

MOESM4 of Overexpression of Rab11-FIP2 in colorectal cancer cells promotes tumor migration and angiogenesis through increasing secretion of PAI-1

Additional file 4: Figure S4. The expression of PAI-1 was also detected by IHC in the tissue samples. We found that the expression of PAI-1 was positively correlated with the expression of Rab11-FIP2 in the tissue samples (r = 0.527, p < 0.001)

Patient-reported outcome measures in functional dyspepsia: a systematic review and COSMIN analysis

Abstract Background Functional dyspepsia (FD) as a type of disorders of brain-gut interaction (DBGI), patient self-reporting of its symptoms becomes an important component of clinical outcome assessment. We performed a systematic review using Consensus Based Standards for the Selection of Health Measurement Instruments (COSMIN) guidelines to identify the best available patient-reported outcome measure (PROM) of FD. Methods The study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We searched four databases with no date limit, looking for previously confirmed PROMs for evaluating FD symptoms. An overall rating was then assigned based upon COSMIN guidelines, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to assess the level of evidence for psychometric properties of included PROMs. Results Thirty articles covering outcome indicators of 24 patient reports were included. The Leuven Postprandial Distress Scale (LPDS) showed adequate content validity and moderate quality evidence of adequate internal consistency to generate an A recommendation. Conclusion LPDS is currently the most recommended PROM for patient self-reported FD symptoms. However, it fails to assess two important areas of cross-cultural validity/ measurement invariance and measurement error. Future research can be continuously improved on this basis

An Accelerated Method for Protecting Data Privacy in Financial Scenarios Based on Linear Operation

With the support of cloud computing technology, it is easier for financial institutions to obtain more key information about the whole industry chain. However, the massive use of financial data has many potential risks. In order to better cope with this dilemma and better protect the financial privacy of users, we propose a privacy protection model based on cloud computing. The model provides four levels of privacy protection according to the actual needs of users. At the highest level of protection, the server could not access any information about the user and the raw data, nor could it recover the computational characteristics of the data. In addition, due to the universality of the mathematical principle of linear operators, the model could effectively protect and accelerate all models based on linear operations. The final results showed that the method can increase the speed by 10 times, compared with the privacy protection method that only uses local computing power instead of the cloud server. It can also effectively prevent the user’s privacy from being leaked with relatively minimal delay cost, compared with no privacy protection method. Finally, we design a multi-user scheduling model to deploy the model in a real scenario, which could maximise server power and protect user privacy as well

Maternal TDP-43 interacts with RNA Pol II and regulates zygotic genome activation

Abstract Zygotic genome activation (ZGA) is essential for early embryonic development. However, the regulation of ZGA remains elusive in mammals. Here we report that a maternal factor TDP-43, a nuclear transactive response DNA-binding protein, regulates ZGA through RNA Pol II and is essential for mouse early embryogenesis. Maternal TDP-43 translocates from the cytoplasm into the nucleus at the early two-cell stage when minor to major ZGA transition occurs. Genetic deletion of maternal TDP-43 results in mouse early embryos arrested at the two-cell stage. TDP-43 co-occupies with RNA Pol II as large foci in the nucleus and also at the promoters of ZGA genes at the late two-cell stage. Biochemical evidence indicates that TDP-43 binds Polr2a and Cyclin T1. Depletion of maternal TDP-43 caused the loss of Pol II foci and reduced Pol II binding on chromatin at major ZGA genes, accompanied by defective ZGA. Collectively, our results suggest that maternal TDP-43 is critical for mouse early embryonic development, in part through facilitating the correct RNA Pol II configuration and zygotic genome activation