The Research Of KIF14,miR-376b-3p And 3 Kinds Of Circrna Involved In Inflammatory Response During Priming Phase Of Rat Liver Regeneration

It is generally believed that liver regeneration(LR)induced by 2/3 partial hepatectomy(PH)in rats was divided into three phases: priming(0 h?6 h after PH),progression(6 h?72 h after PH)and termination(72 h?168 h after PH).Among them,the inflammatory response was one of the key events during the priming phases of LR.Related inflammatory factors maintain the inflammatory response within a reasonable range that promote cell proliferation without causing serious damage.Studies have shown that LR was regulated by many factors including circularRNA(circRNA),which is an endogenous non-codingRNA and participates in the regulation of a variety of physiological activities,including cell proliferation,inflammatory response,cell differentiation and apoptosis.High-throughput sequencing technology with the characteristics of high detection speed and large-scale enables researchers to rapidly expand the information.Combined with bioinformatics analysis,it enable uncover key molecules in diseases.In view of this,this paper attempted to elucidate the merchanism underlying the ceRNA on the inflammatory response during the priming phase of rat LR by this method.For this purpose,competing endogenousRNA(ceRNA)expression was globally analyzed by high-throughput sequencing.It showed that a total of 13,999 circRNAs,921 miRNAs and 13,251 mRNAs were detected at 0 h and 6 h after PH,among which2843 circRNAs,348 miRNAs and 2479 mRNAs were significantly differentially expressed.Subsequently,by querying the National Coalition Building Institute(NCBI)website and using innovative pathway analysis(IPA)software,766 mRNAs related to inflammation were screened from the 2479 differentially expressed mRNAs,and 64 mRNAs belonging to transcription factors were further discovered.According to the principle of reverse(mRNA?miRNA?circRNA)that circRNA regulating miRNA and miRNA regulating mRNA,241 circRNAs,110 miRNAs and 766 mRNAs related to inflammatory responses were predicted by searching websites such as mi RWalk and Target Scan.Among the above-mentioned TF related to inflammation,we selected the key gene KLF14 mRNA by GSEA software,and found that it was highly expressed at 6 h after PH and closely related to inflammation.Based on the speculation,this paper focused the molecular mechanism of regulating LR inflammatory homeostasis during the priming phases with miRNA and circRNA.Cytoscape was used to visualize the KLF14 mRNA related ceRNA interaction network,and found that KLF14 mRNA formed 272 interactions with 18 miRNAs and 99 circRNAs at 0 h,and 406 interactions with 39 miRNAs and 128 circRNAs at 6 h.Next,we used the Cistrome Data Browser websites search and IPA software to get the downstream genes regulated by KLF14.Finally,based on the principle of ceRNA comprehensive analysis,1 miRNA,3 circRNAs upstream of KLF14 mRNA,and 2 inflammatory response-related downstream genes of KLF14 were screened out.It was disclosed that this may regulate downstream gene expression through the circRNA-miRNAKLF14 mRNA key axis to keep the inflammatory response of hepatocytes at a stable level.All in all,this paper further studied the expression and action correlation of circRNA,miRNA and mRNA in the inflammatory response during the priming phase of rat LR,and analyzed the molecular mechanism of ceRNA regulating the homeostasis of inflammatory response.These findings provide a theoretical basis and research idea for molecular mechanism of rat LR and liver tissue engineering.