Alcohol consumption promotes colorectal cancer by altering intestinal permeability.

OBJECTIVE: The purpose of this study was to uncover the potential impact of alcohol consumption on the tumorigenesis of colorectal cancer (CRC) and the underlying mechanism. PATIENTS AND METHODS: Overall survival was compared in CRC patients either with alcohol consumption or not. Subsequently, a mouse model of CRC was established by azoxymethane (AOM) administration. Tumor number and size were compared in CRC mice fed with Lieber-DeCarli liquid diet or normal diet. At last, pathological differences in cell proliferation, apoptosis, inflammation, and intestinal permeability, in intestines harvested from CRC mice fed with Lieber-DeCarli liquid diet or normal diet were assessed. RESULTS: It was found that the prognosis was worse in CRC patients with alcohol consumption. In CRC mice fed with Lieber-DeCarli liquid diet, more tumor tissues were found than those in the controls. Besides, alcohol consumption remarkably impaired intestinal permeability, making it easier for bacteria to invade epithelial cells. Moreover, oral gavage of probiotics markedly improved intestinal permeability and reduced tumor number in CRC mice fed with Lieber-DeCarli liquid diet. CONCLUSIONS: Probiotics can inhibit the development of alcohol-induced CRC by protecting intestinal permeability.

Overexpression of XIST facilitates cell proliferation, invasion and suppresses cell apoptosis by reducing radio-sensitivity of glioma cells via miR-329-3p/CREB1 axis.

OBJECTIVE: Glioma is a malignant brain cancer capable of spreading to the microenvironment. Long non-coding RNA (lncRNA) X inactive specific transcript (XIST) was recognized as a significant regulator in many cancers. However, the molecular mechanism of XIST in glioma cell radio-sensitivity requires further exploration. PATIENTS AND METHODS: The expression of XIST, microRNA (miR)-329-3p and cyclic AMP response element-binding protein 1 (CREB1) was evaluated by quantitative Real-time polymerase chain reaction (qRT-PCR). Cell viability and apoptosis were examined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and flow cytometry, respectively. Transwell assay was performed to detect cell invasion. Protein expression of gamma-H2AX (γ-H2AX) and CREB1 was determined by Western blot. The correlation between miR-329-3p and XIST or CREB1 was determined by dual-luciferase reporter assay. Animal models were established by subcutaneously injecting U251 cells transfected with sh-XIST and sh-NC. RESULTS: XIST and CREB1 were overexpressed whereas miR-329-3p was low-expressed in glioma tumors and cells compared with the normal counterparts. XIST knockdown inhibited cell proliferation, invasion and induced cell apoptosis by enhancing cell sensitivity to X-ray radiation in glioma. Then, we discovered that miR-329-3p directly interacted with XIST or CREB1 in glioma. In addition, miR-329-3p inhibitor abolished XIST silencing-induced regulatory effects on cell proliferation, apoptosis, invasion, and radio-sensitivity. Meanwhile, miR-329-3p inhibitor counteracted CREB1 silencing-induced inhibition on cell progression and facilitation on radio-sensitivity in glioma. Moreover, we found that XIST could increase CREB1 expression by sponging miR-329-3p. Animal experiments revealed that XIST silencing restrained tumor growth in vivo. CONCLUSIONS: XIST accelerates cell proliferation, invasion and inhibits cell apoptosis by repressing radio-sensitivity of glioma via enhancing CREB1 expression through sponging miR-329-3p, representing prospective methods for glioma treatment.