Rui Deng

miR-219-5p plays a tumor suppressive role in colon cancer by targeting oncogene Sall4

Sall4 is a novel oncogene found upregulated in several malignancies including colon cancer. However, its upstream regulatory miRNA is still undefined. miR-219-5p is regarded as a tumor-related miRNA in cancer research. Nevertheless, its actual role of whether inhibiting or promoting tumorigenesis is unclear in colon cancer. Potential interaction between Sall4 and miR-219-5p is predicted by TargetScan. CCK-8 test was used for evaluation of cell proliferation and cell survival rates. Western blot analysis and real-time PCR were applied for detection of target molecules. Luciferase assay was a direct confirmation of mutual interaction. Wound healing assay and transwell assay were conducted for cell migration and invasion tests. Flow cytometry was used for cell apoptosis analysis. Tissue specimens and cell lines were explored for miR-219-5p inhibition on colon cancer proliferation, migration, invasion, apoptosis and drug resistance by targeting Sall4. The results show that miR-219-5p inhibited carcinogenesis of colon cancer by targeting oncogene Sall4.

Helicobacter Pylori Promote B7-H1 Expression by Suppressing miR-152 and miR-200b in Gastric Cancer Cells

The most common cause of gastric cancer is infection with helicobacter pylori (HP), but the associated molecular mechanism is not well understood. In the present study, we found a marked increase in the expression of B7-H1, a member of the B7 co-stimulatory family of molecules that bind to programmed death-1 (PD-1) and play a critical immunoregulatory role in the cell-mediated immune response, in HP-positive gastric cancer tissue. Infection of cultured gastric cancer cells with HP promoted B7-H1 expression and inhibited miR-152 and miR-200b expression. We further demonstrated that these two miRNAs targeted B7-H1 mRNA and suppressed B7-H1 expression in gastric cancer cells. Finally, B7-H1 expression was found to correlate with miR-152 and miR-200b levels in gastric tumor tissues from human patients. Our findings suggest a novel mechanism by which HP infection promotes gastric cancer and also suggest potential targets, i.e., miR-152 and miR-200b, for the prevention and treatment of gastric cancer.

Clinicopathologic Features of Gastric Schwannoma: 8-Year Experience at a Single Institution in China.

AbstractTo explore the clinicopathologic characteristics, diagnosis, treatment, and prognosis of gastric schwannoma in the imatinib era.The clinicopathologic characteristics and postoperative outcomes of patients diagnosed with gastric schwannoma at our institution between January 2007 and February 2015 were retrospectively collected and analyzed.The main patient complaint was epigastric pain or discomfort. Tumor sizes ranged from 15 to 80 mm (mean, 57.1 mm). In 17 patients, the tumors were located in the body of the stomach. A total of 20 patients were preoperatively misdiagnosed with a gastrointestinal stromal tumor. The rate of correct preoperative diagnosis was only 3.3%. All patients underwent surgical resection and showed strong S-100 protein positivity. Laparoscopic surgery for gastric schwannoma was associated with less blood loss and a shorter postoperative hospital stay than open surgery (P < 0.01). Total 28 patients were disease free without recurrence or metastasis at a median follow-up time of 50 months.Gastric schwannoma is often preoperatively misdiagnosed as gastric gastrointestinal stromal tumor. Laparoscopic resection of gastric schwannoma is considered safe and effective, and it may be the preferred surgery for most small- and moderate-sized tumors. The long-term outcome is excellent, as this type of neoplasm is uniformly benign.

Autophagy protects gastric mucosal epithelial cells from ethanol-induced oxidative damage via mTOR signaling pathway

Alcohol abuse is an important cause of gastric mucosal epithelial cell injury and gastric ulcers. A number of studies have demonstrated that autophagy, an evolutionarily conserved cellular mechanism, has a protective effect on cell survival. However, it is not known whether autophagy can protect gastric mucosal epithelial cells against the toxic effects of ethanol. In the present study, gastric mucosal epithelial cells (GES-1 cells) and Wistar rats were treated with ethanol to detect the adaptive response of autophagy. Our results demonstrated that ethanol exposure induced gastric mucosal epithelial cell damage, which was accompanied by the downregulation of mTOR signaling pathway and activation of autophagy. Suppression of autophagy with pharmacological agents resulted in a significant increase of GES-1 cell apoptosis and gastric mucosa injury, suggesting that autophagy could protect cells from ethanol toxicity. Furthermore, we evaluated the cellular oxidative stress response following ethanol treatment and found that autophagy induced by ethanol inhibited generation of reactive oxygen species and degradation of antioxidant and lipid peroxidation. In conclusion, these findings provide evidence that ethanol can activate autophagy via downregulation of the mTOR signaling pathway, serving as an adaptive mechanism to ameliorate oxidative damage induced by ethanol in gastric mucosal epithelial cells. Therefore, modifying autophagy may provide a therapeutic strategy against alcoholic gastric mucosa injury. Impact statement The effect and mechanism of autophagy on ethanol-induced cell damage remain controversial. In this manuscript, we report the results of our study demonstrating that autophagy can protect gastric mucosal epithelial cells against ethanol toxicity in vitro and in vivo. We have shown that ethanol can activate autophagy via downregulation of the mTOR signaling pathway, serving as an adaptive mechanism to ameliorate ethanol-induced oxidative damage in gastric mucosal epithelial cells. This study brings new and important insights into the mechanism of alcoholic gastric mucosal injury and may provide an avenue for future therapeutic strategies.

Reduced proliferation and increased apoptosis of the SGC‑7901 gastric cancer cell line on exposure to GDC‑0449

The sonic hedgehog (Shh) pathway is known to be vital in embryonic development and cancer propagation due to its irreplaceable role in cell proliferation and differentiation. GDC‑0449, a basal cell skin cancer target drug approved by the Food and Drugs Administration, is a smoothened (Smo)-specific antagonist. Although it has been clinically verified as a valid drug for the treatment of skin and pancreatic cancer, the application of GDC‑0449 in gastric cancer requires further investigation. In the present study, high-glucose Dulbeccos modified Eagles medium with 10% fetal bovine serum was used for routine SGC‑7901 cell line culture. A Cell Counting Kit‑8 assay was employed for determination of the reproductive rate of the cells. Flow cytometry was performed to determine the apoptosis status of the SGC‑7901 cell line through Q4 analysis. Reverse transcription-quantitative polymerase chain reaction and Western blot analyses were used as target molecule detection vehicles. As expected, GDC‑0449 reduced the expression levels of Shh‑associated molecules, including Smo and gli1, compared with the blank group. The rate of cell proliferation was markedly limited and was accompanied by an increase in the apoptotic rate following GDC‑0449 exposure. In addition, further investigations confirmed B cell lymphoma‑2 (Bcl‑2) as the downstream molecular mechanism of GDC‑0449 efficacy. Of note, representatives of the cancer stem cell (CSC) surface marker, CD44 and CD133, demonstrated a similar trend to the Smo restriction observed. By repressing the expression of Bcl‑2, GDC‑0449 inhibited the normal proliferation of SGC‑7901 cells, and accelerated the apoptotic rate of the cells. It may also alter CSC properties due to the reduction in the expression of surface markers.

Clinicopathologic features and prognosis of primary gastrointestinal stromal tumor patients under 35 years of age: A 10‐year retrospective study

To investigate gastrointestinal stromal tumor (GIST) clinicopathologic characteristics in young adults.