Overexpression of Dermokine-α enhances the proliferation and epithelial-mesenchymal transition of pancreatic tumor cells.

Pancreatic cancer is a prevalent malignancy of the digestive system and a major cause of cancer-associated deaths. Previous studies have shown that mutation in the dermokine-ß (DMKN-ß) gene causes pancreatic and colorectal cancer. The role of the carboxy-terminal domain of DMKN-ß and dermokine-α (DMKN-α) genes in cancer tumorigenesis. Herein, the role of DMKN-α in pancreatic cancer (PC) tumorigenesis and the mechanisms underlying this process were investigated. Differentially expressed genes between PC and matched normal cells were identified through RNA-seq analysis, and the corresponding protein expression levels were verified using Western blot analysis. In vivo tumor formation experiment was also performed in nude mice. We found that the DMKN-α gene was overexpressed in cancerous pancreatic cell lines compared to normal pancreatic cell lines. CCK-8, colony formation, RTCA test, wound healing, as well as transwell test showed that the overexpression of DMKN-α enhanced the proliferation, migration, invasion, and EMT of PC cells. In vivo assays confirmed that DMKN-α promotes tumorigenesis. The findings of this study show that DMKN-α is a potential oncogene for pancreatic cancer.

Isocorydine suppresses doxorubicin-induced epithelial-mesenchymal transition via inhibition of ERK signaling pathways in hepatocellular carcinoma.

Doxorubicin (DOX) is a conventional and effective chemotherapeutic used in the treatment of hepatocellular carcinoma (HCC). However, doxorubicin administration may induce EMT, which results in the development of chemoresistance in HCC. Recent studies report that Isocorydine (ICD) selectively inhibits human cancer stem cells (CSCs), which have an important role in the development of chemoresistance. In this study, we observed that ICD co-administration enhanced DOX cytotoxicity in HCC cells, enabling the inhibition of DOX-induced epithelial-mesenchymal transition (EMT). Microarray data analysis revealed substantially decreased ERK signaling after ICD treatment. Additionally, we observed decreased IC50 for DOX upon ERK knockdown. Finally, we confirmed the enhanced efficacy of treatment with a combination of DOX and ICD in xenograft models. Collectively, the present study unveils the benefit of using DOX in combination with ICD for chemotherapy against HCC, revealing a novel potential anti-cancer strategy.

The C825T Polymorphism of the G-Protein ß3 Gene as a Risk Factor for Functional Dyspepsia: A Meta-Analysis.

Background. Functional dyspepsia (FD) is a functional upper gastrointestinal disorder with significant morbidity and medical costs. Previous studies investigated the association of G-protein ß3 (GNB3) genetic polymorphisms with FD but with inconsistent results. Therefore, we performed a meta-analysis to derive a precise estimation of the relationship between GNB3 polymorphisms and FD. Methods. We searched different databases including PubMed, EMBASE, CNKI, and the Ovid Library to gather eligible studies on GNB3 polymorphisms and FD. The association was assessed by the odds ratio (OR) with 95% confidence intervals (CI). Results. We identified 12 studies with 1109 cases and 2853 controls for the analysis. We found no associations of GNB3 C825T polymorphism with FD in the overall population (T versus C, OR = 1.06, 95% CI: 0.96-1.18, P = 0.26; TT versus CC + CT, OR = 1.16, 95% CI: 0.97-1.39, P = 0.11; TT + CT versus CC, OR = 1.01, 95% CI: 0.77-1.31, P = 0.96; TT versus CC, OR = 1.15, 95% CI: 0.93-1.44, P = 0.20). Subgroup analyses by genotyping method indicated that the magnitude of association was strengthened for additive model (OR = 1.15, 95% CI: 1.07-2.24, P = 0.02). Sensitivity analysis did not reveal significant associations under all models. Conclusions. This meta-analysis demonstrates that GNB3 C825T polymorphism may not be a risk factor for FD.

Clinicopathological significance and potential drug target of O6-methylguanine-DNA methyltransferase in colorectal cancer: a meta-analysis.

Emerging evidence indicates that O(6)-methylguanine-DNA methyltransferase (MGMT) is a candidate for tumor suppression in several types of human tumors including colorectal cancer (CRC). However, the correlation between MGMT hypermethylation and clinicopathological characteristics of CRC remains unclear. In this study, we conducted a systematic review and meta-analysis to quantitatively evaluate the effects of MGMT hypermethylation on the incidence of CRC and clinicopathological characteristics. A comprehensive literature search was done from Web of Science, the Cochrane Library Database, PubMed, EMBASE, CINAHL, and the Chinese Biomedical Database for related research publications written in English and Chinese. Methodological quality of the studies was also evaluated. Analyses of pooled data were performed with Review Manager 5.2. Odds ratio (OR) and hazard ratio (HR) were calculated and summarized, respectively. Final analysis from 28 eligible studies was performed. MGMT hypermethylation is found to be significantly higher in CRC than in normal colorectal mucosa, the pooled OR from 13 studies including 1085 CRC and 899 normal colorectal mucosa, OR = 6.04, 95 % confidence interval (CI) = 4.69-7.77, p < 0.00001. MGMT hypermethylation is also significantly higher in colorectal adenoma than in normal colorectal mucosa, but it is significantly less compared to that in CRC patients. Interestingly, MGMT hypermethylation is correlated with sex status and is significantly higher in female than in male. MGMT hypermethylation is also associated with high levels of microsatellite instability (MSI). The pooled HR for overall survival (OS) shows that MGMT hypermethylation is not associated with worse survival in CRC patients. The results of this meta-analysis suggest that MGMT hypermethylation is associated with an increased risk and high levels of MSI and may play an important role in CRC initiation. However, MGMT hypermethylation may play an important role in the early stage of CRC progression and development, as well as having limited value in prediction of prognosis in CRC patients. We also discussed that MGMT may serve as a potential drug target of CRC.