[High KHSRP expression promotes gastric adenocarcinoma metastasis: the mediating role of the JAK1/STAT3 signaling axis].

OBJECTIVE

To investigate the regulatory effect of KHSRP on progression of gastric adenocarcinoma and the role of the JAK1/STAT3 signaling axis in mediating its effect.

METHODS

KHSRP mRNA expression level was detected using qRT-PCR in 120 pairs of gastric adenocarcinoma and adjacent tissues, 4 gastric adenocarcinoma cell lines (MKN-28, HGC-27, CRL-5822, and SNU-1) and normal human gastric mucosal GES-1 cells. In HGC-27 cells with KHSRP knockdown and SNU-1 cells with KHSRP overexpression, cell proliferation, migration, invasion and expression levels of JAK/STAT were evaluated using CCK-8 assay, Transwell migration and invasion assays, and Western blotting. In BALB/c-nude mice, HGC-27 cells with KHSRP knockdown and SNU-1 cells overexpressing KHSRP were injected either subcutaneous or via the tail vein to observe subcutaneous xenograft growth and lung metastasis of the tumor cells.

RESULTS

Gastric adenocarcinoma tissues and cell lines all showed significantly increased KHSRP expression as compared with the adjacent tissues and GES-1 cells. In HGC-27 cells, KHSRP knockdown significantly inhibited cell proliferation, migration and invasion, while KHSRP overexpression enhanced the malignant behaviors of SNU-1 cells. In nude mice, inoculation of HGC-27 cells with KHSRP knockdown resulted in smaller tumor volume and weight, slower cell proliferation rate and fewer lung metastatic foci, and KHSRP-overexpressing SNU-1 cells produced the opposite results. KHSRP knockdown in HGC-27 cells significantly down-regulated the expression levels of JAK1 and STAT3, which were obviously increased in KHSRP-overexpressing SNU-1 cells.

CONCLUSION

High expressions of KHSRP promote progression and metastasis of gastric adenocarcinoma possibly by regulating the JAK1/STAT3 signaling axis.