Nuclear matrix-associated protein SMAR1 regulates alternative splicing via HDAC6-mediated deacetylation of Sam68

Significance Multiple studies highlight the role of various proteins in regulation of alternative splicing; however, the regulatory role of distinct posttranslational modifications during alternative splicing that contribute to tumorigenesis is enigmatic. Here we report a previously unidentified noncanonical mechanism of regulation of alternative splicing modulated by deacetylation of RNA-binding protein Sam68 (Src-associated substrate during mitosis of 68 kDa) via Scaffold/matrix-associated region-binding protein 1 (SMAR1)–histone deacetylase 6 (HDAC6) complex. SMAR1 in complex with HDAC6 maintains Sam68 in a deacetylated state. We observed that ERK-1/2–dependent phosphorylation of SMAR1, knockdown of SMAR1, or loss of heterozygosity facilitates CD44 variant exon inclusion via Sam68 acetylation and thus confers invasive and metastatic potential in breast tumor cells. Our findings provide key insights into regulation of alternative splicing and the potential for therapeutic intervention during tumor metastasis. </jats:p

Environmental factors in benign migratory glossitis and psoriasis: Retrospective study of the association of emotional stress and alcohol and tobacco consumption with benign migratory glossitis and cutaneous psoriasis

BackgroundThe association between benign migratory glossitis (BMG) and psoriasis (PS) has been reported in the literature.ObjectiveThis study aimed to determinate the environmental factors related to BMG and PS and to investigate their interactions.MethodsThe study population included 129 patients with PS, 399 patients with BMG and a control group (CG) of 5472 individuals with neither PS nor BMG. the environmental factors evaluated in this study included alcohol and tobacco consumption and emotional stress. the Pearson's chi-squared test was used for analysing the association of the environmental factors with PS and BMG.ResultsThe prevalence of alcohol consumption in the PS group was significantly higher than that in the CG. Tobacco consumption had a weak negative association with the BMG group. With respect to the PS group, no statistically significant association was observed. Emotional stress was the most important factor in the two study groups. Emotional stress and alcohol use together presented a higher incidence in the study groups than in the CG. Emotional stress and tobacco consumption together had a three times higher incidence in the PS group than in the BMG group. the association of emotional stress, alcohol and tobacco consumption in the PS group was four times higher than that in the CG.LimitationsThis study was limited by the lack of the information about frequency, type and length time of use of tobacco and alcohol, and by difficult to measure stress thought self-report questionnaire.ConclusionThe interactions between PS and environmental factors differ from those between BMG and environmental factors. These differences among interactions may be responsible for different forms of manifestations of these diseases, considering being both the same disease.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Univ Marilia UNIMAR, Discipline Dermatol, Sch Med, Marilia, SP, BrazilBeneficent Assoc Univ Hosp Unimar ABHU, São Paulo, BrazilFed Univ São Paulo UNIFESP, Dept Biosci, São Paulo, SP, BrazilCtr Higher Educ Dracena CESD, Res Ctr, Dracena, SP, BrazilUniv Fed Fluminense, Dept Pathol, Rio de Janeiro, BrazilReaserch Ctr Assoc Educ & Culture Vilhena Assoc V, Vilhena, RO, BrazilFed Univ São Paulo UNIFESP, Dept Dermatol, São Paulo, SP, BrazilFed Univ São Paulo UNIFESP, Dept Biosci, São Paulo, SP, BrazilFed Univ São Paulo UNIFESP, Dept Dermatol, São Paulo, SP, BrazilWeb of Scienc