Construction of a novel mRNA-miRNA-lncRNA network and identification of potential regulatory axis associated with prognosis in colorectal cancer liver metastases.

Liver metastasis is a leading cause of death in patients with colorectal cancer (CRC). Increasing evidence demonstrates that competing endogenous RNA (ceRNA) networks play important roles in malignant cancers. The purpose of this study was to identify molecular markers and build a ceRNA network as a significant predictor of colorectal liver metastases (CRLM). By integrated bioinformatics analysis, we found that apolipoprotein C1 (APOC1) was upregulated in CRLM and associated with prognosis in patients with CRC and thereby established an APOC1-dependent ceRNA network. By survival analysis, expression analysis, and correlation analysis of each element in the ceRNA network, we identified that ZEB1-AS1, miR-335-5p and APOC1 regulated each other. We further experimentally confirmed that ZEB1-AS1 promoted a CRC progression via regulating the expression of miR-335-5p that controlled the expression of APOC1. Our findings indicate that the ZEB1-AS1-miR-335-5p-APOC1 ceRNA regulatory network is significantly valuable for better prognosis of patients with CRC and as a new therapeutic target for the treatment of CRLM.

circBANP promotes colorectal cancer growth and metastasis via sponging let-7d-5p to modulate HMGA1/Wnt/ß-catenin signaling.

Colorectal cancer (CRC) is one of the most common and deadly cancers, and the incidence of CRC is on the rise. Due to the lack of early diagnosis method and high metastasis of the disease, the prognosis of CRC remains very poor. Exploring the underlying molecular mechanisms of CRC is very necessary for effective therapy. In this study, we investigated the function of circBANP in CRC. The results showed that circBANP was elevated in both CRC tissues and cells and its level positively correlated with the stage of CRC. Knockdown of circBANP greatly suppressed the epithelial-mesenchymal transition (EMT) process and CRC cell proliferation, migration, and invasion. In addition, knockdown of circBANP inhibited CRC tumor growth and metastasis in vivo. Further, circBANP directly bound to let-7d-5p and regulated CRC development via acting as a let-7d-5p sponge. Let-7d-5p directly targeted HMGA1 and thus circBANP/let-7d-5p regulated Wnt/ß-catenin signaling via HMGA1. Collectively, circBANP promotes CRC development and metastasis via acting as a let-7d-5p sponge to regulate HMGA1/Wnt/ß-catenin signaling, providing a potential biomarker and therapeutic target for the management of CRC.

Girdin Knockdown Increases Gemcitabine Chemosensitivity to Pancreatic Cancer by Modulating Autophagy.

Chemotherapy is crucial for the treatment of pancreatic cancer (PC). Gemcitabine (GEM) as the first-line chemotherapy drug has a high resistance rate. Increasing the sensitivity of gemcitabine is currently the objectives and challenges of this study. Our previous study showed Girdin was closely related to the progression and prognosis of PC, indicating that Girdin may be associated with chemosensitivity. In the current study, we use recombinant adenovirus to specifically knockdown Girdin in PC cell lines to determine the effect of Girdin in the process of gemcitabine chemosensitivity. Autophagy is one of the pathways affecting the gemcitabine chemosensitivity in PC. Further research validated that Girdin may activate autophagy by interacting with autophagy protein p62/SQSTM1, which could enhance chemotherapy resistance to gemcitabine in PC. Down-regulation of Girdin may therefore increase gemcitabine chemosensitivity in PC. Our results reveal that Girdin acted as a negative regulator of gemcitabine chemosensitivity in PC. Increased autophagy activity caused by abnormally high Girdin expression may be one of the main factors for the reduction in chemosensitivity, which may provide new perspectives on understanding chemosensitization in PC.

Down-regulation of miRNA-196b expression inhibits the proliferation, migration and invasiveness of HepG2 cells while promoting their apoptosis via the PI3K/Akt signaling pathway.

The purpose of this study was to investigate the effects of microRNA-196b (miRNA-196b) on proliferation, migration, invasiveness and apoptosis of hepatocellular carcinoma cell line (HepG2), and the mechanism involved.   MiRNA-196b inhibitor or negative control were transfected into HepG2 cells, while empty liposome vector was used as normal control. The results of transfection were assessed using real-time quantitative polymerase chain reaction (qRT-PCR). Cell proliferation, migration, invasiveness and apoptosis were determined using cell counting kit 8 (CCK-8), scratch test, Transwell invasion assay, and flow cytometric analysis, respectively. The expressions of PIK3, Akt and p-Akt proteins were determined using Western blotting. The HepG2 cells were also treated with PI3K/Akt signaling pathway inhibitor LY294002, and its effect on cell proliferation, migration, invasion, and apoptosis, and expressions of PIK3, Akt, and p-Akt proteins were determined. The results of RT-PCR showed that the relative expression of miRNA-196b in the inhibitor group (0.42 ± 0.13) was significantly lower than that in the blank control group (0.96 ± 0.10) and the negative control group (1.01 ± 0.32) (p < 0.05). The miRNA-196b inhibitor significantly and time-dependently reduced the invasiveness, proliferation migration abilities of HepG2 cells, while promoting their apoptosis (p < 0.05). The expressions of PIK3 and p-Akt proteins were significantly down-regulated in the inhibitor group, when compared with normal and negative control groups (p < 0.05). However, there were no significant differences in the expression of Akt protein among the groups (p > 0.05). After treatment of HepG2 cells with PI3K/Akt signaling pathway inhibitor LY294002, the proliferative, migratory and invasive abilities of cells in the treatment group were significantly enhanced, while cell apoptosis was significantly reduced (p < 0.05). Similarly, the protein expressions of PIK3 and p-Akt in the non-treatment group was significantly upregulated, relative to the treatment group (p < 0.05), but there was no significant difference in the expression of Akt protein between the two groups (p > 0.05). Downregulation of miRNA-196b expression inhibits the proliferation, migration and invasiveness of HepG2 cells, while promoting their apoptosis via a mechanism involving the PI3K/Akt signaling pathway.

Giant ventral hernia simultaneously containing the spleen, a portion of the pancreas and the left hepatic lobe: A case report.

BACKGROUND: Ventral hernia, also known as incisional hernia, is a common complication of previous surgery. The contents of ventral hernia may include omentum, preperitoneal fat, small intestine or colon. However, ventral hernia with protrusion of more than two parenchymal organs simultaneously is extremely rare, and its repair is very complex and difficult. Surgeons should make a comprehensive assessment based on their own experience and the individual characteristics of the hernia. In addition, psychological therapy should be emphasized in the whole treatment process. CASE SUMMARY: We report a rare case of asymptomatic giant ventral hernia for 15 years in a 21-year-old female. The patient underwent umbilical hernia repair at the age of 1 year. Approximately 5 years later, ventral hernia recurred and repair with Mesh was performed, but the operation failed due to postoperative infection, and a huge mass appeared in the left abdominal wall. The mass increased gradually with the development and maturity of the body. Computerized tomography scan demonstrated that the patient's total spleen, part of the pancreas and left lobe of the liver were simultaneously herniated through the abdominal incisional hernia. As the patient was unable to endure the inconvenience of life and the potential risk of spleen or liver rupture, she underwent a ventral hernia repair with Mesh at our hospital. The operation was successful and the patient had a good recovery. During a 3-mo follow-up, the patient remained asymptomatic and the appearance of the surgical incision was greatly improved. CONCLUSION: Ventral hernia is a common complication of abdominal surgery. Ventral hernia with protrusion of more than two parenchymal organs simultaneously is extremely rare. Surgeons should pay attention to the psychological treatment while restoring the abdominal physiological function in ventral hernia patients.

Girdin interaction with vimentin induces EMT and promotes the growth and metastasis of pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant cancer of the digestive tract that has a high potential for metastasis and a poor prognosis. Girdin was first reported in 2005 as an actin­binding protein and was designated as Akt­phosphorylation enhancer (APE); thus, Girdin has been revealed to have an important role in regulating cancer development. There is additional evidence indicating that Girdin is associated with cell proliferation, migration, invasion and survival in certain cancers. However, the potential mechanisms involving Girdin and mobility in pancreatic cancer have not been elucidated. In the present study, it was revealed that Girdin was highly expressed in pancreatic cancer tissue and was associated with tumor grade. The present study, to the best of our knowledge, is the first aimed at investigating the unknown role of Girdin in PDAC metastasis. A short hairpin RNA for Girdin (sh­Girdin) was successfully constructed with recombinant adenoviral vectors to suppress the expression of Girdin in pancreatic cancer cell lines (PANC­1 and BXPC­3). The silencing efficiency of the Girdin shRNA was determined by RT­qPCR and western blot analysis, and decreased Girdin expression in the cytoplasm was revealed by immunofluorescence detection. Then, sulforhodamine B (SRB) and colony formation assays were used to confirm that the knockdown of Girdin inhibited proliferation in vitro, and Transwell assays were used to examine the influence of Girdin knockdown on cellular mobility. Animal experiments also confirmed that silencing the expression of Girdin in pancreatic cancer cells inhibited the growth and metastasis of pancreatic cancer in vivo. Transforming growth factor­ß (TGF­ß) is a common inducer of epithelial­mesenchymal transition (EMT) and can effectively induce EMT in PDAC. Notably, TGF­ß­treated cells exhibited changes in the classic biological markers of EMT. The expression of E­cadherin, a marker of the epithelial phenotype, increased, and the expression of N­cadherin and vimentin, markers of the interstitial phenotype, decreased in response to sh­Girdin. According to these experiments, Girdin may affect pancreatic cancer progression and development by interacting with vimentin. Therefore, there is evidence indicating that Girdin could be designated as a prognostic biological indicator and a candidate therapeutic target for pancreatic cancer.

The influencing factors and spatial spillover effects of CO2 emissions from transportation in China.

CO2 emissions from transportation (TC) are one of the main causes of global climate change. China faces particularly severe pressures and challenges in transportation carbon reduction. Based on the panel data of 30 provinces in China from 2000 to 2015, this study explored the influencing factors and spatial spillover effects of TC by estimating spatial panel data models. It found that China's TC will continue to increase in the future, because the increase in per capita gross domestic product (GDP) is the primary driving force to accelerate the growth of TC, but an increasing proportion of tertiary industry (PTI) in the national economy will help reduce the growth in emissions. Moreover, urban road density (URD) and per capita highway mileage (PHM) are the other two major factors promoting the growth of TC. In contrast, urban population density (UPD) has a negative direct impact on per capita CO2 emissions from transportation (PTC) but also has a larger positive spatial spillover effect, which indicates that these three factors should be properly planned and controlled. Meanwhile, we should actively advocate the development of urban public transport because it plays an important role on reducing TC. The conclusions provide important inspiration and a scientific basis for formulating policies to effectively curb the growth of CO2 emissions in China.

Long noncoding RNA DANCR regulates proliferation and migration by epigenetically silencing FBP1 in tumorigenesis of cholangiocarcinoma.

Recently, long noncoding RNAs (lncRNAs) have been shown to play significant regulatory roles in human tumorigenesis. However, the biological function of lncRNAs in cholangiocarcinoma (CCA) remains largely unknown. In this study, DANCR was shown to be significantly upregulated in CCA. DANCR regulated the proliferation and migration of CCA cells in vitro. Moreover, downregulation of DANCR suppressed CCA cells proliferation in vivo. RNA-seq revealed that DANCR knockdown preferentially affected genes linked with cell proliferation and cell differentiation. Furthermore, mechanistic investigation validated that DANCR could bind EZH2 and modulate the histone methylation of promoter of FBP1, thereby regulating CCA cells growth and migration. Taken together, these results demonstrated the significant roles of DANCR in CCA and may provide a theoretical basis for clinical diagnosis and treatment of CCA.

Insulin promotes proliferation of pancreatic ductal epithelial cells by increasing expression of PLK1 through PI3K/AKT and NF-κB pathway.

Pancreatic cancer has a poor prognosis. Many epidemiological evidence show that diabetes is closely related to the occurrence of pancreatic cancer. The concentration of insulin in pancreas local tissues is higher than that in systemic circulation. In this study, we aimed to investigate the effect of insulin on pancreatic duct epithelial cells and identify the potential mechanisms. We found that insulin promoted the proliferation of pancreatic duct epithelial cells in the dependent of increased PLK1. Furthermore, PI3K/AKT and NF-κB pathway were involved in this process. By using PI3K/AKT inhibitor LY294002 and NF-κB shRNA, the increased PLK1 was reversed and cells proliferation was inhibited. Additionally, immunofluorescence analysis revealed the co-localization between PLK1 and ß-catenin. We showed that insulin can promote the increased expression of ß-catenin dependent on PLK1. This study showed that insulin may promotes cell proliferative vitality of pancreatic ductal epithelial cells by inducing PLK1 through PI3K/AKT and NF-κB pathway; The upregulation of PLK1 may reduce the degradation of ß-catenin. This may be one of the mechanisms by which T2DM promotes pancreatic cancer.

Intermittent abdominal pain accompanied by defecation difficulties caused by Chilaiditi syndrome: A case report.

We report a case of intermittent lower abdominal pain and distension accompanied by defecation difficulties for 3 years due to Chilaiditi syndrome in a 59-year-old male. Before admission to our hospital, the patient had undergone gastroscopy, which showed gastritis and duodenitis, and colonoscopy, which showed cecum deformation and cicatricial changes of the mucous membrane in the colon hepatic flexure. A computed tomography (CT) scan of the abdomen at our hospital confirmed right hepatic atrophy and interposition of the colon. Moreover, CT simulation endoscopy identified cystic dilatation in the colon hepatic flexure with the widest diameter of 8.2 cm. The patient was diagnosed with Chilaiditi syndrome. As the patient was unable to endure his defecation difficulties, he underwent a laparoscope-assisted right hemicolectomy. The patient had a good recovery. During the follow-up period of 9 mo, the patient remained symptom-free.