MiR-200a-3p promotes gastric cancer progression by targeting DLC-1.

Gastric cancer (GC) is one of the most common malignancies, ranking the third highest mortality rate worldwide. Due to the insidious symptoms and difficulty in early detection, patients with GS were mostly in the middle and late stages when they were diagnosed. Although ontogenetic or tumor-suppressive effects of miRNA-200a-3p have been demonstrated, the exact mechanism underlying GC is not clear. Therefore, the expression, effect, and mechanism of miRNA-200a-3p in GC progression were systematically investigated in this study. qRT-PCR, Western blotting, and immunohistochemical staining were applied to investigate the miRNA-200a-3p and deleted in liver cancer 1 (DLC-1) expression. Cell viability, proliferation, apoptosis, migration, and invasion capabilities of GC cells were assessed using cell counting kit-8 (CCK-8) colorimetry, EdU integration, flow cytometry, wound healing, and the transwell assay. The relationship between miRNA-200a-3p and tumor growth was investigated by tumor xenograft assay in vivo. A dual-luciferase reporter assay was estimated to verify the connection between miR-200-3p and DLC-1. The results showed that miRNA-200a-3p expression was significantly increased in both GC tissues and cells. Furthermore, via DLC-1, miRNA-200a-3p promotes tumor growth and development. miRNA-200a-3p, by targeting DLC-1, can function as an oncogene in GC cells. Collectively, our findings indicated that the miRNA-200a-3p/DLC axis might provide a theological basis for potential improvements in GC treatment strategies.

Transcription factor HOXC10 activates the expression of MTFR2 to regulate the proliferation, invasion and migration of colorectal cancer cells.

HOXC10 and mitochondrial fission regulator 2 (MTFR2) have been reported to be abnormally expressed in multiple types of cancer tissues. However, the effects of HOXC10 and MTFR2 on colorectal cancer (CRC) remain poorly understood. Therefore, the present study aimed to investigate the expression of HOXC10 and MTFR2 in CRC tissues and cells, and analyze their effects on CRC cell proliferation, invasion and migration. Reverse transcription­quantitative PCR and western blotting were used to detect the expression levels of MTFR2 and HOXC10 in tissues and cells. To investigate the association between MTFR2 and HOXC10, short hairpin RNA­MTFR2 and overexpression vector­HOXC10 were transfected into the cells, respectively. Furthermore, western blotting was performed to detect the expression levels of invasion­associated proteins. The proliferation, clone formation, invasion and migration of colorectal cancer cells were in turn analyzed by the Cell Counting Kit­8, clone formation, wound healing and Transwell assays. Japan Automotive Software Platform and Architecture software predicted the binding sites between HOXC10 and MTFR2, which was confirmed by the dual­luciferase reporter assay and chromatin immunoprecipitation. The present study demonstrated that HOXC10 and MTFR2 mRNA and protein expression levels were significantly upregulated in CRC tissues and cells. MTFR2 knockdown significantly inhibited CRC cell proliferation, clone formation, invasion and migration. Furthermore, HOXC10 was shown to interact with MTFR2. HOXC10 overexpression was able to significantly reverse the inhibitory effects of MTFR2 knockdown on CRC cells. In conclusion, HOXC10 overexpression activated MTFR2 expression to enhance the proliferation, clone formation, invasion and migration of CRC cells.

The prognostic value of serum bilirubin in colorectal cancer patients with surgical resection.

PURPOSE: Serum bilirubin plays an important role in antioxidant and anticancer processes. The inverse association between serum bilirubin and cancer risk have been widely reported in multiple cancers. The aim of this retrospective study was to investigate the prognostic impact of serum bilirubin in colorectal cancer patients undergoing surgical resection. METHODS: The value of serum bilirubin including total bilirubin, direct bilirubin, and indirect bilirubin were tested at pre-operatively in 330 colorectal cancer patients. The optimal cut-off values for these three biomarkers were determined by X-tile program. The relationship between serum bilirubin and outcomes were examined using Kaplan-Meier curves log-rank test, univariate and multivariate cox regression. Moreover, a number of risk factors were used to form a nomogram for evaluating risk of survival. RESULTS: The optimal cut-off points of serum total bilirubin, direct bilirubin, and indirect bilirubin were 19.5 µmol/L, 5.0 µmol/L and 8.1 µmol/L, respectively. Elevated total bilirubin and direct bilirubin were significantly associated with overall survival in surgical colorectal cancer patients. Additionally, predictive nomogram including total bilirubin and direct bilirubin for overall survival was established for predicting overall survival in surgical colorectal cancer patients. CONCLUSIONS: These findings indicated that preoperative elevated total bilirubin and direct bilirubin could be considered as independent prognostic biomarkers for poor overall survival of colorectal cancer patients.

Association Between Polymorphisms in Gastric Cancer Related Genes and Risk of Gastric Cancer: A Case-Control Study.

Gastric cancer has the second highest incidence among all the malignancies in China, just below lung cancer. Gastric cancer is likewise one of the main sources of cancer related passings. Gastric cancer therefore remains a huge threat to human health. The primary reason is absence of high sensitivity and specificity for early detection while the pathogenesis of GC is stayed muddled. During the last few decades, a lot of GC related genes have been identified. To find candidate GC related variant in these GC related genes, we conducted this case-control study. 29 tagSNPs located in 7 GC related genes were included. 228 gastric cancer patients and 299 healthy controls were enrolled. Significant differences were found between the genotype frequencies of EFNA1 rs4971066 polymorphism between gastric cancer patients and healthy controls. The result indicated that ephrin-A1 tagSNP rs4971066 GT/TT genotypes was significantly associated with reduced susceptibility of gastric cancer development.

Identification and validation of tumor microenvironment-related prognostic biomarkers in breast cancer.

BACKGROUND: Stromal cells and immune cells in tumor microenvironment (TME) have been reported to have significant value in the diagnosis and prognosis of cancers. We aimed to identify key biomarkers predicting survival in the TME of breast cancer. METHODS: Cell type enrichment analysis was performed to estimate cell scores using the xCell method with gene expression data from public database. Least absolute shrinkage and selection operator (LASSO) regression was used to identify key signature from the cell scores. RESULTS: Totally, 50 cells in TME had different scores between 1,078 breast cancer tissues and 112 adjacent normal tissues. We identified a 4-cell signature predicting breast cancer survival, including myocytes, natural killer T cell (NKT), conventional dendritic cell (cDC) and sebocytes, which was validated in the test set. Further analysis showed that cDC score was a key signature predicting prognosis of breast cancer. cDC score was significantly associated with molecular classification and stage of breast cancer, as well as expression level of Ki67. Spearman's correlation analysis found that cDC score was inversely correlated with the expression level of HER2. High cDC score may predicate better pathological complete response rate. Mechanism analysis indicated high cDC score was associated with elevated immune activity; IL-2 was a key gene associated with high cDC score; and Breast cancer patients with high IL-2 expression had a longer survival time. CONCLUSIONS: In conclusion, cDC score was a key signature predicting prognosis for breast cancer. cDCs may exert antitumor effects by upregulating IL-2.

Preparation, in vitro and in vivo evaluation of budesonide loaded core/shell nanofibers as oral colonic drug delivery system.

Budesonide (BUD) loaded ethylcellulose (EC)-core/Eudragit S100-shell nanofibers (BUD-core/shell-NFs) have been successfully prepared using a coaxial electrospinning technique. The drug encapsulation efficiency was 90.48%. SEM and TEM analysis showed that fine core-shell structured nanofibers with an average diameter 190 nm and uniform core diameters 74 nm were prepared. The BUD-loaded Eudragit S100/EC composite nanofibers (BUD-NFs) were prepared using a blend electrospinning method and used as a control. In vitro release tests in HCl 0.1 N, phosphate buffer solutions pH 6.8 and 7.4 were studied. Moreover, the colon-specific characteristics were directly proven in vivo by the content of BUD in different segments of the gastrointestinal (GI) tract in rats after oral administration. Taken together, the results confirmed that BUD-core/shell-NFs had desired pH-dependent drug release profile, displayed a sustained and complete drug release in the colon, as well as protected BUD from being released completely in the upper portion of the GI tract. Compared with BUD-NFs, the BUD-core/shell-NFs have much better potential to be developed as oral colon-specific drug delivery system (OCDDS) to overcome the disadvantages of current oral formulations of BUD.