LncRNAs Expression Profiles Reflect The Types Of Microbes In Gut Tissues And Penguin Promotes P53 Degradation In CRC

Backward :Specific composition of intestinal bacteria may be associated with various of human diseases,such as IBD and colorectal cancer.Previous studies have shown that lncRNAs also plays an important role in the development of colorectal cancer.Howerver,it was not clear how gut microbes act with lncRNAs in colorectal cancer.Here we show a link between long non-coding RNA(lncRNA)expression and gut microbes.The p53 tumor suppressor is frequently inactivated in most human tumors,and reactivating the wild-type p53 represents a promising therapeutic strategy.Methods: By repurposing exon microarrays and comparing the lncRNA expression profiles between germ-free,conventional and different gnotobiotic mice,we revealed subgroups of lncRNAs that were specifically enriched in each condition.A nearest shrunken centroid methodology was applied to obtain lncRNA based signatures to identify mice in different conditions.Apoptosis and proliferation of colorectal cancer cell line were detected after penguin si RNAs interference and plasmid transfection.Western blot,co IP assay was designed to explore the regulation mechanism of penguin on p53.A transgenic mouse model over-expressing human morn3(penguin)was established to find out the effect of morn3(penguin)on the expression of p53 and its downstream genes in vivo.Besides,the effect of morn3(penguin)on the growth of transplanted tumor in nude mice was observed in xenograft model.Results: The lncRNA-based prediction model successfully identified different gnotobiotic mice from conventional and germ-free mice,and also discriminated mice harboring transplanted microbes from fecal samples of mice or zebra fishes.To achieve optimal prediction accuracy,fewer lncRNAs were required in the prediction model than protein-coding genes.Taken together,our study demonstrated the effecacy of lncRNA expression profiles in discriminating the types of microbes in the gut.Knockdown of penguin in CRC cells promote apoptosis and inhibit the proliferation in vitro experiments.The Western blot results showed that overexpression of exogenous penguin would accelerate a direct interaction with p53 and promote the ubiquitination and degradation of p53.In the transgenic mouse model,penguin can reduce the expression level of p53 and p21.Besides,overexpression of penguin could promote tumor growth in xenograft model of nude mice.Conclusion : These results also provide a resource of gut microbe-associated lncRNAs for the development of lncRNA biomarkers and the identification of functional lncRNAs in host-microbes interactions.Therefore,targeting morn3(penguin)may reactivate wild-type p53 in CRC while having no adverse effect in normal somatic tissues.