HBO1 induces histone acetylation and is important for non-small cell lung cancer cell growth.

We examined the expression and the potential biological function of HBO1 in non-small cell lung cancer (NSCLC). TCGA and Oncomine databases showed that HBO1 transcripts were elevated in NSCLC. Furthermore, in local NSCLC tumor tissues HBO1 expression was higher than that in matched adjacent lung tissues. In primary and immortalized NSCLC cells, HBO1 shRNA robustly inhibited cell viability, proliferation and migration. Moreover, HBO1 knockout by CRISPR/Cas9 induced significant anti-tumor activity in NSCLC cells. Conversely, ectopic HBO1 overexpression in primary NSCLC cells increased proliferation and migration. H3-H4 histone acetylation and expression of several potential oncogenic genes (CCR2, MYLK, VEGFR2 and OCIAD2) were significantly decreased in NSCLC cells with HBO1 silencing or knockout. They were however increased after HBO1 overexpression. Intratumoral injection of HBO1 shRNA-expressing adeno-associated virus hindered the growth of A549 cell xenografts and primary NSCLC cell xenografts in nude mice. H3-H4 histone acetylation as well as expression of HBO1 and HBO1-dependent genes were decreased in HBO1-silenced NSCLC xenograft tissues. An HBO1 inhibitor WM-3835 potently inhibited NSCLC cell growth. Together, HBO1 overexpression promotes NSCLC cell growth.

Silencing SIX1 by miR-7160 inhibits non-small cell lung cancer cell growth.

The homeoprotein SIX1 is upregulated in non-small cell lung cancer (NSCLC) and associated with NSCLC tumorigenesis and progression. We identified microRNA-7160 (miR-7160) as a SIX1-targeting miRNA. RNA immunoprecipitation results confirmed a direct binding between miR-7160 and SIX1 mRNA in NSCLC cells. In the primary and established NSCLC cells, forced overexpression of miR-7160 downregulated SIX1 and inhibited cancer cell growth, proliferation, migration and invasion. Furthermore, miR-7160 overexpression induced apoptosis activation in NSCLC cells. Conversely, miR-7160 inhibition elevated SIX1 expression and enhanced NSCLC cell progression in vitro. Restoring SIX1 expression, by an untranslated region-depleted SIX1 expression construct, reversed miR-7160-induced anti-NSCLC cell activity. CRISPR/Cas9-inudced knockout of SIX1 mimicked miR-7160-induced actions and produced anti-NSCLC cell activity. In vivo, intratumoral injection of miR-7160-expressing lentivirus downregulated SIX1 mRNA and inhibited NSCLC xenograft growth in severe combined immunodeficient mice. Significantly, miR-7160 expression is downregulated in human NSCLC tissues and is correlated with SIX1 mRNA upregulation. Collectively, miR-7160 silenced SIX1 and inhibited NSCLC cell growth in vitro and in vivo.

The Relationship between Depression and Asthma: A Meta-Analysis of Prospective Studies.

BACKGROUND: Previous studies have suggested that asthmatic patients often have comorbid depression; however, temporal associations remain unclear. OBJECTIVES: To determine whether depression predicts asthma and, conversely, whether asthma predicts depression. METHODS: A literature search was conducted without language restrictions using Pubmed, Embase, Cochrane and PsycINFO for studies published before January, 2015. Papers referenced by the obtained articles were also reviewed. Only comparative prospective studies with reported risk estimates of the association between depression and asthma were included. In order to investigate whether one of these conditions was predictive of the other, studies were excluded if enrolled participants had pre-existing depression or asthma. A random-effects model was used to calculate the pooled risk estimates for two outcomes: depression predicting asthma and asthma predicting depression. RESULTS: Seven citations, derived from 8 cohort studies, met our inclusion criteria. Of these, six studies reported that depression predicted incident adult-onset asthma, including 83684 participants and 2334 incident cases followed for 8 to 20 years. Conversely, two studies reported that asthma predicted incident depression. These studies involved 25566 participants and 2655 incident cases followed for 10 and 20 years, respectively. The pooled adjusted relative risks (RRs) of acquiring asthma associated with baseline depression was 1.43 (95% CI, 1.28-1.61) (P<0.001). The adjusted RRs for acquiring depression associated with baseline asthma was 1.23 (95% CI, 0.72-2.10) (P = 0.45). CONCLUSIONS: Depression was associated with a 43% increased risk of developing adult-onset asthma. However, asthma did not increase the risk of depression based on limited studies. Further prospective studies ascertaining the true association between asthma and subsequent risk of depression are warranted.