PGC-1α/SNAI1 axis regulates tumor growth and metastasis by targeting miR-128b in gastric cancer

Peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1 alpha) is a transcriptional coactivator that has been characterized as master regulators of mitochondrial biogenesis. It has been reported that aberrant regulation of PGC-1 alpha is involved in a variety of human cancers. However, whether PGC-1 alpha is involved in the regulation of tumor growth and metastasis in gastric cancer (GC) remains unknown. In the present study, we found that the expression of PGC-1 alpha was upregulated in GC tissues and GC cell lines. Inhibition of PGC-1 alpha inhibited cell viability, migration, and invasion, and promoted cell apoptosis of GC cells. Furthermore, inhibition of PGC-1 alpha downregulated the SNAI1 expression, whereas upregulated microRNA (miR)-128b expression. The expression of SNAI1 was upregulated and the expression of miR-128b was downregulated in GC tissues. We further found that there was a positive correlation between PGC-1 alpha and SNAI1 expression, and a negative correlation between PGC-1 alpha and miR-128b expression or between SNAI1 and miR-128b expression in GC tissues. Moreover, PGC-1 alpha inhibition-induced increased miR-128b expression, and PGC-1 alpha overexpression-induced decreased miR-128b expression were both markedly suppressed by SNAI1 overexpression. In addition, SNAI1 overexpression or miR-128b inhibition partly reversed the effects of PGC-1 alpha inhibition in GC cells. Furthermore, inhibition of PGC-1 alpha suppressed the tumor growth in a nude mouse model, which may be related with the dysregulation of SNAI1 and miR-128b. In conclusion, these data indicate that the PGC-1 alpha/SNAI1/miR-128b axis plays a vital role in GC via regulating cell viability, migration, invasion, and apoptosis.