Recently, intriguing new roles for some small nucleolar RNA host genes (SNHGs) in cancer have emerged. In the present study, a panel of SNHGs was profiled to detect aberrantly expressed SNHGs in gastric cancer (GC). The expression of SNHG5 was significantly downregulated in GC and was significantly associated with the formation of a tumor embolus and with the tumor, node and metastasis stage. SNHG5 was a long non-coding RNA, which was a class of non-coding RNA transcripts longer than 200 nucleotides. SNHG5 suppressed GC cell proliferation and metastasis in vitro and in vivo. Furthermore, SNHG5 exerted its function through interacting with MTA2, preventing the translocation of MTA2 from the cytoplasm into the nucleus. SNHG5 overexpression led to significant increases in the acetylation levels of histone H3 and p53, indicating that SNHG5 might affect acetylation by trapping MTA2 in the cytosol, thereby interfering with the formation of the nucleosome remodeling and histone deacetylation complex. This study is the first to demonstrate that SNHG5 is a critical and powerful regulator that is involved in GC progression through trapping MTA2 in the cytosol. These results imply that SNHG5 may be a novel therapeutic target for the treatment of GC.

Blood pressure (BP) is a major risk factor for cardiovascular disease and more than 200 genetic loci associated with BP are known. Here, we perform a multi-stage genome-wide association study for BP (max N = 289,038) principally in East Asians and meta-analysis in East Asians and Europeans. We report 19 new genetic loci and ancestry-specific BP variants, conforming to a common ancestry-specific variant association model. At 10 unique loci, distinct non-rare ancestry-specific variants colocalize within the same linkage disequilibrium block despite the significantly discordant effects for the proxy shared variants between the ethnic groups. The genome-wide transethnic correlation of causal-variant effect-sizes is 0.898 and 0.851 for systolic and diastolic BP, respectively. Some of the ancestry-specific association signals are also influenced by a selective sweep. Our results provide new evidence for the role of common ancestry-specific variants and natural selection in ethnic differences in complex traits such as BP.

As one of the most common intracranial tumors, pituitary tumor is associated with high morbidity. Effective therapy is currently not available for some pituitary tumors due to the largely undefined pathological processes of pituitary tumorigenesis. In this study, hyperactivation of mammalian/mechanistic target of rapamycin (mTOR) signaling was observed in estrogen-induced rat pituitary tumor and mTOR inhibitor rapamycin blocked the tumor development. Pituitary knockout of either mTOR signaling pathway negative regulator Tsc1 or Pten caused mouse pituitary prolactinoma, which was abolished by rapamycin treatment. Mechanistically, the expression of pituitary tumor transforming gene 1 (PTTG1) was upregulated in an mTOR complex 1-dependent manner. Overexpressed PTTG1 was crucial in hyperactive mTOR-mediated tumorigenesis. mTOR-PTTG1 signaling axis may be targeted for the treatment of tumors with mTOR hyperactivation.

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Although death receptor 6 (DR6) is aberrantly expressed in certain cancer cell lines, its function, signaling pathway and potential clinical significance in tumor progression are not well characterized. We report here that knocking down DR6 in the mouse B16 cell line has no effect on B16 cell death in vitro but suppresses xenograft B16 tumor growth by preventing tumor blood vessel formation in vivo. Deficiency of DR6 changes cytokine expression and secretion; in particular, it inhibits the proinflammatory cytokine interleukin-6 (IL-6), which is able to induce the expression of the angiogenesis-related factors: vascular endothelial growth factor-A, platelet-derived growth factor-β, vascular endothelial growth factor-D and platelet-derived growth factor receptor-α. Further experiments demonstrate that DR6-dependent angiogenesis is involved in the IL-6/P38 MAPK and IL-6/STAT3 pathways. Our novel findings demonstrate for the first time that DR6 expression in B16 cells facilitates tumor growth by accelerating tumor angiogenesis. Moreover, these results suggest that DR6 is involved in three important intracellular pathways that lead to homeostatic angiogenesis in tumor growth.

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