RESUMO
Tumorigenesis in different segments of the intestinal tract involves tissue-specific oncogenic drivers. In the colon, complement component 3 (C3) activation is a major contributor to inflammation and malignancies. By contrast, tumorigenesis in the small intestine involves fatty acid-binding protein 1 (FABP1). However, little is known of the upstream mechanisms driving their expressions in different segments of the intestinal tract. Here, we report that the RNA-binding protein DDX5 binds to the mRNA transcripts of C3 and Fabp1 to augment their expressions posttranscriptionally. Knocking out DDX5 in epithelial cells protected mice from intestinal tumorigenesis and dextran sodium sulfate (DSS)-induced colitis. Identification of DDX5 as a common upstream regulator of tissue-specific oncogenic molecules provides an excellent therapeutic target for intestinal diseases.
Assuntos
Complemento C3/metabolismo , RNA Helicases DEAD-box/metabolismo , Proteínas de Ligação a Ácido Graxo/metabolismo , Animais , Carcinogênese/metabolismo , Colite/induzido quimicamente , Complemento C3/genética , RNA Helicases DEAD-box/fisiologia , Sulfato de Dextrana/efeitos adversos , Células Epiteliais/metabolismo , Proteínas de Ligação a Ácido Graxo/genética , Feminino , Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/genética , Inflamação , Mucosa Intestinal/metabolismo , Intestino Delgado/metabolismo , Intestinos/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Oncogenes/genética , Transdução de SinaisRESUMO
INTRODUCTION: Smoking cessation at any stage of pregnancy can benefit the mother and fetus. Cigarette dependence is a significant factor in women who continue to smoke during pregnancy and accurate assessment of cigarette dependence can be helpful in planning smoking cessation programs. The objective of our study was to investigate the validity of the Fagerstrom Test for Cigarette Dependence (FTCD) and Heaviness of Smoking Index (HSI) as measures of cigarette dependence in the second and third trimesters of pregnancy by comparing them to serum cotinine levels. METHODS: Prospective cohort study of 167 women in their second and third trimester of pregnancy who self-reported cigarette smoking. They were administered the FTCD questionnaire and blood was drawn for cotinine measurements using a direct enzyme linked immunoassay. Linear regression was used to adjust for maternal age, body mass index, gestation, and parity to investigate the association between cotinine levels and the two scores. RESULTS: Both the FTCD and HSI correlated significantly with serum cotinine levels (Spearman coefficient 0.42 and 0.37, respectively, p < .001). The correlation coefficients of both scores were higher in primigravidas (n = 51) compared to multigravidas, but the difference was statistically nonsignificant. Using multiple linear regression, both scores were significantly related to serum cotinine levels. For each unit increase in the FTCD and HSI, the serum cotinine level increased by 21.4 ng/mL (95% confidence interval 10.1-32.7, p <0.001) and 37 ng/mL (95% confidence interval 18.6-55.4, p < 0.001), respectively. CONCLUSIONS: Both the FTCD and HSI can be used to assess cigarette dependence in the second and third trimester of pregnancy. IMPLICATIONS: There is lack of data on the validity of the FTCD and the HSI as markers of cigarette dependence during the second and third trimester of pregnancy. Our study suggests that both the FTCD and HSI perform well in assessing cigarette dependence in the second and third trimester of pregnancy and can be used to plan smoking cessation programs.