4.6 Article

GRB10 is a novel factor associated with gastric cancer proliferation and prognosis

Journal

AGING-US
Volume 15, Issue 9, Pages 3394-3409

Publisher

IMPACT JOURNALS LLC

Keywords

GRB10; gastric cancer; proliferation; prognosis

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GRB10 and its family members GRB7 and GRB14 are important adaptor proteins that regulate cellular functions by interacting with tyrosine kinase receptors and other phosphorus-containing amino acid proteins. Abnormal expression of GRB10 is closely related to cancer occurrence and development. In gastric cancer, high expression of GRB10 is associated with poorer overall survival. Knockdown of GRB10 inhibits proliferation and migration ability in gastric cancer, and miR-379-5p can downregulate GRB10 expression to suppress gastric cancer development. Therefore, miR-379-5p and GRB10 are potential targets for gastric cancer treatment.
GRB10 and its family members GRB7 and GRB14 were important adaptor proteins. They regulated many cellular functions by interacting with various tyrosine kinase receptors and other phosphorus-containing amino acid proteins. More and more studies have shown that the abnormal expression of GRB10 is closely related to the occurrence and development of cancer. In our current research, expression data for 33 cancers from the TCGA database was downloaded for analysis. It was found that GRB10 was up-regulated in cholangiocarcinoma, colon adenocarcinoma, head and neck squamous carcinoma, renal chromophobe, clear renal carcinoma, hepatocellular carcinoma, lung adenocarcinoma, lung squamous carcinoma, gastric adenocarcinoma and thyroid carcinoma. Especially in gastric cancer, the high GRB10 expression was closely associated with poorer overall survival. Further research showed that the knockdown of GRB10 inhibited proliferation and migration ability in gastric cancer. Also, there was a potential binding site for miR-379-5p on the 3 ' UTR of GRB10. Overexpression of miR-379-5p in gastric cancer cells reduced GRB10-regulated gastric cancer proliferation and migration capacity. In addition, we found that tumor growth was slower in a mice xenograft model with knock down of GRB10 expression. These findings suggested that miR-379-5p suppresses gastric cancer development by downregulating GRB10 expression. Therefore, miR-379-5p and GRB10 were expected to be potential targets for the treatment of gastric cancer.

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