MicroRNA let-7b suppresses human gastric cancer malignancy by targeting ING1.

Abstract

MicroRNAs (miRNAs) are important regulators that play key roles in tumorigenesis and tumor progression. In this study, we investigate whether let-7b acts as a tumor suppressor to inhibit invasion and metastasis in gastric cancers. We analyzed the expression of let-7b in 60 pair-matched gastric neoplastic and adjacent non-neoplastic tissues by quantitative real-time polymerase chain reaction. Functional analysis of let-7b expression was assessed in vitro in gastric cancer cell lines with let-7b precursor and inhibitor. The roles of let-7b in tumorigenesis and tumor metastasis were analyzed using a stable let-7b expression plasmid in nude mice. A luciferase reporter assay was used to assess the effect of let-7b on inhibitor of growth family, member 1 (ING1) expression. Real-time PCR showed decreased levels of let-7b expression in metastatic gastric cancer tissues and cell lines that are potentially highly metastatic. Cell invasion and migration were significantly impaired in GC9811-P and SGC7901-M cell lines after transfection with let-7b mimics. Nude mice with xenograft models of gastric cancer confirmed that let-7b could inhibit gastric cancer metastasis in vivo after transfection by the lentivirus pGCsil-GFP- let-7b. Luciferase reporter assays demonstrated that let-7b directly binds to the 3'-UTR of ING1, and real-time PCR and western blotting further indicated that let-7b downregulated the expression of ING1 at the mRNA and protein levels. Our study demonstrates that overexpression of let-7b in gastric cancer can inhibit invasion and migration of gastric cancer cells through directly targeting the tumor metastasis-associated gene ING1. These findings help clarify the molecular mechanisms involved in gastric cancer metastasis and indicate that let-7b modulation may be a bona fide treatment of gastric cancer.