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

Abstract

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.