Colorectal cancer ( CRC ) is the third most commonly diagnosed cancer in both men and women in the USA. However, the underlying molecular mechanisms that drive CRC tumorigenesis are still not clear. Several studies have reported that long noncoding RNA s (lnc RNA s) have important roles in tumor development. Here, we undertook a transcriptome microarray analysis in 6 pairs of CRC tissues and their corresponding adjacent normal tissues. A total of 1705 differentially expressed lnc RNA s were detected in CRC tissues at stages I/ II and III / IV (fold change greater than or equal to 2 or less than or equal to 0.5). Among them, we found that the lnc RNA lung cancer‐associated transcript 1 ( LUCAT 1 ) was upregulated in CRC tissues and was closely associated with poor overall survival of CRC patients, through analysis of clinical data and The Cancer Genome Atlas. Functional studies indicated that LUCAT 1 promoted CRC cell proliferation, apoptosis, migration, and invasion in vitro and in vivo. Furthermore, knockdown of LUCAT 1 rendered CRC cells hypersensitive to oxaliplatin treatment. Mechanistically, bioinformatic analysis indicated that low expression of LUCAT 1 was associated with the p53 signaling pathway. Chromatin isolation by RNA purification followed by mass spectrometry and RNA immunoprecipitation revealed that LUCAT 1 bound with UBA 52 , which encodes ubiquitin and 60S ribosomal protein L40 ( RPL 40). We found that RPL 40 functions in the ribosomal protein‐ MDM 2‐p53 pathway to regulate p53 expression. Taken together, our findings indicate that suppression of LUCAT 1 induces CRC cell cycle arrest and apoptosis by binding UBA 52 and activating the RPL 40‐ MDM 2‐p53 pathway. These results implicate LUCAT 1 as a potential prognostic biomarker and therapeutic target for CRC .

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Background The relationship between disturbances of the gut microbiota and 1,25(OH) 2 D 3 deficiency has been established both in humans and animal models with a vitamin D poor diet or a lack of sun exposure. Our prior study has demonstrated that Cyp27b1 − / − ( Cyp27b1 knockout) mice that could not produce 1,25(OH) 2 D 3 had significant colon inflammation phenotypes. However, whether and how 1,25(OH) 2 D 3 deficiency due to the genetic deletion controls the gut homeostasis and modulates the composition of the gut microbiota remains to be explored. Results 1,25(OH) 2 D 3 deficiency impair the composition of the gut microbiota and metabolite in Cyp27b1 − / − mice, including Akkermansia muciniphila, Solitalea Canadensis , Bacteroides - acidifaciens , Bacteroides plebeius and SCFA production. 1,25(OH) 2 D 3 deficiency cause the thinner colonic mucus layer and increase the translocation of the bacteria to the mesenteric lymph nodes. We also found 1,25(OH) 2 D 3 supplement significantly decreased Akkermansia muciniphila abundance in fecal samples of Cyp27b1 − / − mice. Conclusion Deficiency in 1,25(OH) 2 D 3 impairs the composition of gut microbiota leading to disruption of intestinal epithelial barrier homeostasis and induction of colonic inflammation. This study highlights the association between 1,25(OH) 2 D 3 status, the gut microbiota and the colonic mucus barrier that is regarded as a primary defense against enteric pathogens.

Butyrate is a short-chain fatty acid decomposed from dietary fiber and has been shown to have effects on inhibition of proliferation but induction of apoptosis in colorectal cancer cells. However, clinical trials have yielded ambiguous outcomes with regard to its antitumor activities. In this study, we aimed to explore the molecular mechanisms underlying the sensitivity of colorectal cancer cells to sodium butyrate (NaB). RNA sequencing was used to establish the whole-transcriptome profile in NaB-treated versus untreated colorectal cancer cells. Differentially expressed genes were bioinformatically analyzed to predict their possible involvement in NaB-triggered cell death, and the expression of eight dysregulated genes was validated by quantitative real-time PCR. We found that there were a total of 7192 genes (5720 upregulated and 1472 downregulated, fold-change ≥ 2 or ≤ 0.5 for upregulation or downregulation, q-value < 0.05) differentially expressed in NaB-treated cells as compared with the untreated controls. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis demonstrated that the differentially expressed genes were enriched in DNA replication, cell cycle, homologous recombination, pyrimidine metabolism, mismatch repair, and other signaling pathways and may take part in NaB-induced cell death. Among the identified factors, the MCM2-7 complex might be a target of NaB. Our findings provide an important basis for further studies of the complicate network that might regulate sensitivity of colorectal cancer cells to NaB.

The powerful ability of human amnion-derived mesenchymal stem cells (hAMSCs) to promote angiogenesis suggests that they may facilitate angiogenesis-associated therapeutic strategies. However, the molecular mechanisms underlying hAMSC-induced angiogenesis remain largely unknown. The present study results suggested that enhanced migration and tube formation in human umbilical vein endothelial cells (HUVECs) was induced by conditioned medium from hAMSCs (hAMSC-CM). In addition, culture with this conditioned medium resulted in the increased expression of circular RNA ATP binding cassette subfamily B member 10 (circ-ABCB10) and vascular endothelial growth factor A (VEGFA). In the present study genes related to thecirc-ABCB10/microRNA (miR)-29b-3p/VEGFA pathway were predicted using bioinformatics software, and further investigated using in vitro luciferase reporter assays. Loss-of-function assays were performed using small interfering RNAs (siRNAs). The results suggested that siRNA-silencing of circ-ABCB10 in HUVECs weakened migration and tube formation of HUVECs following hAMSC-CM treatment and reduced the levels of VEGFA expression. Treatment with an miR-29b-3p inhibitor could largely rescue these effects in HUVECs, following circ-ABCB10 silencing. The present study results suggest that the circ-ABCB10/miR-29b-3p/VEGFA pathway may be involved in the pro-angiogenic role of hAMSC-CM in HUVECs.