SNHG20/miR-140-5p/NDRG3 axis contributes to 5-fluorouracil resistance in gastric cancer.

5-fluorouracil (5-FU)-based chemotherapy is the first line treatment for advanced gastric cancer. However, the effectiveness of 5-FU is limited by drug resistance. The N-myc downstream-regulated gene, family member 3 (NDRG3) is a member of the NDRG family and has been implicated in numerous types of cancer. However, the role of NDRG3 in gastric cancer remains unclear. In the present study, NDRG3 mRNA expression in gastric cancer and adjacent normal tissues was analyzed using the Gene Expression Profiling Interactive Analysis web tool. NDRG3 expression was silenced using short hairpin RNAs to examine the effect of NDRG3 on the growth of gastric cancer cells. Potential regulators of NDRG3 were identified using the TargetScan and MicroRNA tools and verified by a luciferase assay and reverse transcription-quantitative PCR analysis. The current study demonstrated that NDRG3 was upregulated in gastric cancer specimens and promoted cell proliferation in gastric cancer cell lines. Furthermore, the present study revealed that the small nucleolar RNA host gene 20 (SNHG20)/microRNA (miR)-140-5p signaling pathway may regulate the expression of NDRG3. SNHG20 was revealed to be involved in mediating resistance to 5-FU in gastric cancer cell lines via NDRG3. In conclusion, the results of the present study suggest that the SNHG20/miR-140-5p/NDRG3 axis may be involved in mediating resistance to 5-FU in gastric cancer.

MMP-1/TIMP-1 expressions in rectal submucosa of females with obstructed defecation syndrome associated with internal rectal prolapse.

OBJECTIVE: To explore the MMP-1/TIMP-1 expressions in rectal submucosa of females with obstructed defecation syndrome (ODS) associated with internal rectal prolapse (IRP). METHODS: Fifty-six female patients with ODS associated with IRP were enrolled as Case group, and 43 female hemorrhoids of stages III-IV without constipation and IRP were enrolled as Control group. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry were performed to test the expressions of MMP-1/TIMP-1 in the rectal submucosa. Western blotting was used to examine protein expressions of MMP-1/TIMP-1 and pro-inflammatory cytokines (IL-6 and TNF-α) in the rectal submucosa. EVG staining was conducted to detect collagen and elastic fibers in rectal submucosa. RESULTS: The increased expression of MMP-1 was negatively linked to the decreased TIMP-1 level in the rectal submucosa of patients with ODS associated with IRP. Besides, the expressions of IL-6 and TNF-α were increased in the Case group as compared with the Control group. Additionally, ODS severity and the pro-inflammatory cytokines was positively linked to MMP-1, but negatively related to TIMP-1 in Case group. EVG staining showed that the area ratios of collagen and elastic fibers were lower in Case group than Control group. Through Pearson's correlation analysis, the area ratios of collagen and elastic fibers were positively associated with MMP-1 expression, but negatively correlated with TIMP-1 expression in rectal submucosa of patients with ODS associated with IRP. CONCLUSION: Elevated MMP-1 and reduced TIMP-1 were found in ODS associated with IRP, which was related to the ODS severity, inflammation and contents of collagen and elastic fibers.