THBS4 predicts poor outcomes and promotes proliferation and metastasis in gastric cancer

Abstract

Gastric cancer (GC), a common and lethal cancer in the world, has a high risk of metastasis. Our study was to explore the effects of THBS4 on GC progress and metastasis and the underlying mechanisms. The proliferations of MGC-803 and BGC-823 cells were analyzed via cell count, MTT, and soft agar colony formation assay. The migration and invasion of transfected GC cells was investigated via transwell migration and invasion assay. The mRNA abundance of THBS4 and KLF9 was detected by quantitative real-time PCR (qPCR). The analysis of Gene Expression Omnibus (GEO) dataset (GSE26253) suggested that THBS4 was up-regulated in recurrent GC patients and was positively correlated with the increase in pathological stage and poor prognosis in GC. THBS4 stimulated the proliferations of GC cells. Moreover, THBS4 overexpression fostered the migration and invasion of GC cells. Further, the bioinformatics analysis of the cancer genome atlas dataset suggested that there may be a positive correlation between THBS4 and KLF9 expression. QPCR analysis proved that transfected with THBS4 overexpression plasmid enhanced KLF9 expression in GC cells. THBS4 mRNA and protein expression were up-regulated in MGC-803 and BGC-823 cells compared to those in non-tumoral gastric cells. KLF9 overexpression significantly stimulated the proliferation and metastasis of MGC-803 and BGC-823 cells. Besides, KLF9 siRNA inhibited the enhanced viability, migration, and invasion of MGC-803 cells caused by the transfection with THBS4 overexpression plasmid. In conclusion, THBS4 had positive effects on GC proliferation and metastasis via targeting KLF9.

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