ABSTRACT
Gastric cancer is a type of cancer that is characterized by high morbidity and mortality rates. Long non-coding RNA (lncRNA) ß-1,3-galactosyltransferase 5-AS1 (B3GALT5-AS1) was previously found to be highly expressed in the serum of patients with gastric cancer. However, the regulatory effects of B3GALT5-AS1 in gastric cancer remain poorly understood. The present study aimed to investigate the effects of B3GALT5-AS1 in gastric cancer cell lines. The expression levels of B3GALT5-AS1 were determined in different gastric cancer cell lines (AGS, HGC-27 and MKN-45) using reverse transcription-quantitative PCR. The potential interaction between B3GALT5-AS1 and casein kinase 2 a1 (CSNK2A1) was evaluated using an RNA binding protein immunoprecipitation and RNA pull down assays. Western blot analysis was performed to measure protein expression levels. Cell Counting Kit-8 assay was utilized to determine cell viability, whilst cell invasion and migration were assessed using Transwell and wound healing assays, respectively. Apoptotic cells were evaluated using TUNEL assays. The results showed that B3GALT5-AS1 expression was upregulated in MKN-45 cells compared with the control group. In addition, B3GALT5-AS1 could bind to CSNK2A1 to regulate its expression. B3GALT5-AS1 knockdown attenuated cell viability, invasion and migration, whilst promoting cell apoptosis. These effects were partly reversed by CSNK2A1 overexpression. Overall, results of the present study revealed that interference with B3GALT5-AS1 impeded gastric cancer cell migration and invasion whilst promoting apoptosis by regulating CSNK2A1 expression. These findings suggested that B3GALT5-AS1 and CSNK2A1 may serve a tumorigenic role in the progression of gastric cancer and serve as therapeutic targets for this type of cancer.
ABSTRACT
BACKGROUND The treatment and nursing of gastric cancer (GC) remains an enormous challenge in clinical practice. Understanding the potential mechanisms of the pathogenesis of GC would improve GC therapy. Long intergenic non-protein-coding RNA 01138 (LINC01138) was reported to promote the progression of hepatocellular carcinoma; however, whether it is involved in GC progression has been unclear. MATERIAL AND METHODS Expressions of LINC01138 and miR-1273e in GC tissues and cell lines were measured by qRT-PCR assay. The interaction between LINC01138 and miR-1273e was predicted by the online tool miRDB, verified by dual-luciferase reporter and RNA pulldown assays. Effects of LINC01138 knockdown or miR-1273e overexpression on cell viability, proliferation, apoptosis, invasion, and migration were evaluated by MTT, colony formation assay, flow cytometry, and Transwell assays. Target genes of miR-1273e were predicted by KEGG analysis, and involvement of the mitogen-activated protein kinase (MAPK) pathway was confirmed by qRT-PCR assay. RESULTS LINC01138 was increased but miR-1273e was decreased in GC tissues and cell lines. Knockdown of LINC01138 suppressed GC cell viability, proliferation, invasion, and migration, and promoted GC cell apoptosis. We demonstrated that LINC01138 contributed to GC progression by directly sponging and inhibiting miR-1273e. Moreover, the MAPK pathway was verified to participate in the promotive effects of LINC01138 on GC progression. CONCLUSIONS LINC01138 activated the MAPK signaling pathway by inhibiting miR-1273e to promote GC cell proliferation, invasion, and migration, and inhibit GC cell apoptosis, suggesting that the LINC01138/miR-1273e/MAPK axis is a promising therapeutic target for GC.
