AC125611.3 promotes the progression of colon cancer by recruiting DKC1 to stabilize CTNNB1.

BACKGROUND AND STUDY AIMS: Previous studies have suggested that lncRNAs impact cancer progression. The lncRNA AC125611.3 (also referred to as RP11-161H23.5) is highly expressed in colon cancer but rarely studied; understanding its regulation may provide novel insights on treating colon cancer. MATERIALS AND METHODS: qRT-PCR was performed to quantify RNAs. CCK-8 and EdU assays were performed to assess cell proliferation. Western blot analysis was used to detect levels of proteins related to cell apoptosis and EMT. Wound healing assay and Transwell invasion assay were conducted to evaluate cell migratory and invasive capabilities, respectively. Luciferase reporter assay, RIP assay, and pull-down assay were used to verify RNA-RNA and RNA-protein interactions. RESULTS: AC125611.3 was highly overexpressed in colon cancer cells. AC125611.3 depletion curbed cell proliferative, invasive, migratory, and EMT processes while enhancing apoptosis. Furthermore, AC125611.3 activated the Wnt signaling pathway in colon cancer cells by regulating catenin beta-1 (CTNNB1). Moreover, AC125611.3 recruited dyskeratosis congenita 1 (DKC1) to stabilize CTNNB1. CONCLUSION: AC125611.3 recruits DKC1 to stabilize CTNNB1 and activate Wnt signaling, thereby promoting the progression of colon cancer.

LINC00538 promotes the progression of colon cancer through inhibiting NKD2 expression.

PURPOSE: The purpose of this study was to explore the possible role and mechanism of LINC00538 in the pathogenesis of colon cancer. METHODS: The expression levels of LINC00538 in 70 pairs of colon cancer tissue samples and adjacent ones were examined by qRT-PCR, and survival analysis of patients was performed according to the result. Meanwhile, colon cancer cell lines were screened. In addition, LINC00538 siRNA was transfected into colon cancer cells using liposome method, and then cell proliferation and cell cycle were examined by CCK8 and EDU assays, while cell apoptosis was detected by flow cytometry. Finally, the mechanism of LINC00538 in colon cancer was further explored by RNA-binding protein immunoprecipitation and chromatin immunoprecipitation. RESULTS: The expression of LINC00538 in colon cancer tissues was remarkably higher than that in normal ones, and the overall survival of patients with colon cancer was negatively correlated with the expression of LINC00538. After transfection of LINC00538 siRNA, the proliferation rate of colon cancer cell lines including HCT116 and RKO cells was weakened, the S phase of the cell cycle was shortened, while the cell apoptosis was elevated. In addition, further mechanism studies demonstrated that LINC00538 can bind to EZH2 and inhibit the expression of NKD2, thereby regulating the proliferation and apoptosis of colon cancer cells. CONCLUSIONS: This study demonstrated for the first time that LINC00538 was highly expressed in colon cancer and was associated with poor prognosis of patients. Knockdown of LINC00538 in colon cancer cell lines was able to inhibit the cell proliferation and cell cycle, while it promoted the apoptosis. It's mechanism of participating in the development of colon cancer may be through the down-regulation of NKD2 and the regulation of EZH2.

HSF-1 is involved in attenuating the release of inflammatory cytokines induced by LPS through regulating autophagy.

Autophagy plays a protective role in endotoxemic mice. Heat shock factor 1 (HSF-1) also plays a crucial protective role in endotoxemic mice by decreasing inflammatory cytokines. The purpose of this study was to determine whether HSF-1 is involved in attenuating the release of inflammatory cytokines in lipopolysaccharide (LPS)-stimulated mice and peritoneal macrophages (PMs) through regulating autophagy activity. Autophagosome formation in HSF-1(+/+) and HSF-1(-/-) mice and PMs stimulated by LPS was examined by Western blotting and immunofluorescence. Lipopolysaccharide-induced autophagy and inflammatory cytokines were examined in HSF-1(+/+) and HSF-1(-/-) PMs treated with 3-methyladenine (3-MA) or rapamycin. Results showed that LPS-induced autophagy was elevated transiently at 12 h but declined at 24 h in the livers and lungs of mice. Higher levels of inflammatory cytokines and lower autophagy activity were detected in HSF-1(-/-) mice and PMs compared with HSF-1(+/+) mice and PMs. Interestingly, LPS-induced release of inflammatory cytokines did not further increase in HSF-1(-/-) PMs treated with 3-MA but aggravated in HSF-1(+/+) PMs. Lipopolysaccharide-induced autophagy did not decrease in HSF-1(-/-) PMs treated with 3-MA but decreased in HSF-1 PMs(+/+). Taken together, our results suggested that HSF-1 attenuated the release of inflammatory cytokines induced by LPS by regulating autophagy activity.

[Dynamic pattern of gene expression in rat hearts responding to transient ischemia/reperfusion detected by cDNA microarray and cluster analysis].

OBJECTIVE: To analyze the pattern of gene expression programs during rat myocardial ischemia/reperfusion at multiple time points. METHODS: Rat model of myocardial ischemia/reperfusion was established by repeating the occlusion and relaxation of left coronary artery. cDNA microarray was used to analyze the pattern of gene expression programs in rat myocardium at 1, 3, 6, 12, 24 hours after reperfusion. SOM cluster analysis was used to identify different cluster of genes in which each cluster had similar expression pattern. RESULTS: Altogether 75, 779, 205, 155, and 166 genes were differentially expressed at 1, 3, 6, 12, 24 hours after the reperfusion respectively. Clusters analysis identified 12 clusters of genes in which each cluster had similar expression pattern. CONCLUSION: Analysis of gene expression pattern revealed sequential induction of subsets of genes that characterize each response.