BACKGROUND/AIMS: To investigate the effect of miR-18a on angiogenesis in gastric cancer. METHODOLOGY: We generated stable cell lines overexpressing miR-18a in SGC-7901 cells. Cell proliferation was assessed by the MTT assay. The effects of miR-18a overexpression on tumor growth and angiogenesis were assessed. Because of the key role of mammalian target of rapamycin (mTOR) signaling in gastric cancer progression, we also tested whether miR-18a overexpression affected the mTOR pathway. RESULTS: Ectopic expression of miR-18a significantly diminished cell proliferation in SGC-7901 cells (p<0.01). miR-18a overexpression significantly retarded SGC-7901 xenograft growth by 71.8% in vivo, and caused a marked reduction in tumor angiogenesis assessed by CD31-stained microvessel count. Western blot analysis of the xenografts showed that miR-18a overexpression substantially reduced the phosphorylation of two mTOR substrates, S6K1 and 4E-BPl, indicative of art inactivation of the mTOR pathway. Accompanying with the mTOR inactivation, the angiogenic factors, hypoxia-inducible factor 1 alpha and vascular endothelial growth factor, were significantly downregulated. CONCLUSIONS: These data highlighted an important role for miR-18a in controlling gastric cancer growth and angiogenesis, therefore offering a possible therapeutic strategy against this malignancy.
BACKGROUND/AIMS: To investigate the effect of miR-18a on angiogenesis in gastric cancer. METHODOLOGY: We generated stable cell lines overexpressing miR-18a in SGC-7901 cells. Cell proliferation was assessed by the MTT assay. The effects of miR-18a overexpression on tumor growth and angiogenesis were assessed. Because of the key role of mammalian target of rapamycin (mTOR) signaling in gastric cancer progression, we also tested whether miR-18a overexpression affected the mTOR pathway. RESULTS: Ectopic expression of miR-18a significantly diminished cell proliferation in SGC-7901 cells (p<0.01). miR-18a overexpression significantly retarded SGC-7901 xenograft growth by 71.8% in vivo, and caused a marked reduction in tumor angiogenesis assessed by CD31-stained microvessel count. Western blot analysis of the xenografts showed that miR-18a overexpression substantially reduced the phosphorylation of two mTOR substrates, S6K1 and 4E-BPl, indicative of art inactivation of the mTOR pathway. Accompanying with the mTOR inactivation, the angiogenic factors, hypoxia-inducible factor 1 alpha and vascular endothelial growth factor, were significantly downregulated. CONCLUSIONS: These data highlighted an important role for miR-18a in controlling gastric cancer growth and angiogenesis, therefore offering a possible therapeutic strategy against this malignancy.
Authors: Amanda L Treece; Daniel L Duncan; Weihua Tang; Sandra Elmore; Douglas R Morgan; Ricardo L Dominguez; Olga Speck; Michael O Meyers; Margaret L Gulley Journal: Lab Invest Date: 2016-03-07 Impact factor: 5.662
Authors: Ioana Berindan-Neagoe; Paloma del C Monroig; Barbara Pasculli; George A Calin Journal: CA Cancer J Clin Date: 2014-08-07 Impact factor: 508.702
Authors: Fredy O Beltrán-Anaya; Alberto Cedro-Tanda; Alfredo Hidalgo-Miranda; Sandra L Romero-Cordoba Journal: Front Physiol Date: 2016-08-08 Impact factor: 4.566