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.

MicroRNA-192-5p Promote the Proliferation and Metastasis of Hepatocellular Carcinoma Cell by Targeting SEMA3A

“…25,26 An abnormal expression of miRNAs played important roles in cell migration and invasion capacity by regulating target genes in SP cells. [27][28][29] In this study, CSC-like SP cells from HCCLM3 cell line were subjected to miRNA profiling. As compared with non-SP cells, 50 upregulated and 63 downregulated miRNAs were identified in SP cells.…”

Screening of exosomal microRNAs from colorectal cancer cells

“…This is the first study to describe the full range of miRNAs present in both HCT-116 and HT-29 CRC cell secreted exosomes, demonstrating a large range of miRNAs some of which have well described roles in cancer pathogenesis, and others which have only recently been discovered. Among the most highly expressed miRNAs in both CRC cell line exosomes are several which have previously described roles in gastrointestinal cancers (miR-10b-3p, let7b-5p, miR-378c, miR-145-5p)[21][22][23][24]. In addition, included in the most highly expressed are some miRNAs with little or no available data regarding their association with disease states, associated gene targets or functional roles.These miRNAs may represent new targets as biomarkers worthy of further investigation.…”

Tensor decomposition-based unsupervised feature extraction applied to matrix products for multi-view data processing

“…As the relation between mRNAs identified and breast cancer metastasis can be shown, it is necessary to demonstrate the relationship between the miRNAs identified and breast cancer metastasis. Research of the litertature showsthat all seven miRNAs identified when type I tensors were considered(let-7b [ 53 ], miR-125b [ 54 – 56 ], miR-143 [ 57 – 64 ], miR-145 [ 61 , 62 , 65 – 68 ], miR-21 [ 69 – 73 ], miR-22 [ 74 – 78 ] and miR-99a [ 32 , 79 ]), were reported to be related to metastasis.…”