Construction of a mitochondrial-associated protein DRP1 and a lung cancer-associated protein Erbb4 combined regulatory network

ObjectiveThis research was to establish a mitochondrial-related Drp1 gene and a lung cancer-related Erbb4 gene to participate in the regulatory network of lung cancer cell apoptosis, and to provide theoretical support for mitochondria to participate in tumor regulation.MethodThe GO and KEGG methods were used to construct the regulatory networks of lung cancer related Drp1 and Erbb4 proteins that involved in the apoptosis of tumor cells, and to combine with the Bayesian network theory to screen out the largest possible action path acting on this network; The information about Drp1 in Oncomine database was collected, and the data in current database were analyzed twice. The role of Drp1 in lung cancer was meta-analyzed.ResultA regulatory network of Drp1 and Erbb4 involved in the apoptosis of tumor cells was successfully constructed; the optimal pathway was optimized using Bayesian theory; a total of 446 different types of research results were collected in the Oncomine database, of which there were 18 studies with statistical differences in Drp1 expression, 13 studies with increased Drp1’s expression, and 5 studies with decreased expression. Compared with the control group, Drp1 was expressed in lung cancer tissues highly (P < 0.05).ConclusionEstablishment and optimization of mitochondrial-related Drp1 and tumor-related Erbb4 genes involved in the regulation of apoptosis of cancer cells. It was proposed that Drp1 was expressed in lung cancer tissues highly through in-depth excavation of tumor-associated gene information in the Oncomine gene chip database.     

Establishment of optimal regulatory network of colorectal cancer based on p42.3 protein

Objective: to establish regulatory network of colorectal cancer involving p42.3 protein and to provide theoretical evidence for deep functional exploration of p42.3 protein in the onset and development of colorectal cancer. Methods: with protein similarity algorithm, reference protein set of p42.3 cell apoptosis was built according to structural features of p42.3. GO and KEGG databases were used to establish regulatory network of tumor cell apoptosis involving p42.3; meanwhile, the largest possible working pathway that involves p42.3 protein was screened out based on Bayesian network theory. Besides, GO and KEGG were used to build regulatory network on early diagnosis gene markers for colorectal cancer including WWOX, K-ras, COX-2, p53, APC, DCC and PTEN, at the same time, a regulatory network of colorectal cancer cell apoptosis which involves p42.3 was established. Results: cell apoptotic regulatory network that p42.3 participates in primarily consists of Bcl-2 family genes and the largest possible pathway is p42.3 → FKBP → Bcl-2 centered as FKBP protein. Combined with colorectal cancer regulatory network that involves early diagnosis gene markers, it can be predicted that p42.3 is most likely to regulate the colorectal cancer cell apoptosis through FKBP → Bcl-2 → Bax → caspase-9 → caspase-3 pathway. Conclusion: the colorectal cancer apoptosis network based on p42.3 established in the study provides theoretical evidence for deep exploration of p42.3 regulatory mechanism and molecular targeting treatment of colorectal cancer.     

血清NGF、BDNF、GFAP水平与老年血管性痴呆严重程度的相关性分析

目的:探讨血清神经生长因子(Nerve Growth Factor,NGF)、脑源性神经营养因子(Brain Derived Neural Nutrition Factor, BDNF)、胶质纤维酸性蛋白(Glial Fibrillary Acidic Protein,GFAP)水平与老年血管性痴呆严重程度的相关性。方法:选择我院2016年1月至2018年12月收治的81例老年血管性痴呆患者,根据简易精神状态检查表(MMES)评分将其分为三组,以MMSE评分21～26分者为轻度组(26例),10～20分者为中度组(28例),0～9分者为重度组(27例),同时选择来院体检的50例健康者作为对照组,检测和比较各组的血清NGF、BDNF、GFAP水平,分析血清NGF、BDNF、GFAP水平与老年血管性痴呆患者MMSE分值的相关性。结果:老年血管性痴呆者的血清NGF、GFAP水平明显高于对照组(P0.05),血清BDNF水平明显低于对照组(P0.05)。轻度组、中度组、重度组的血清NGF、GFAP、BDNF水平对比差异均有统计学意义(P0.05):NGF水平:轻度组中度组重度组,BDNF水平:轻度组中度组重度组;GFAP水平:轻度组中度组重度组。血清NGF、BDNF水平与MMSE分值评分呈显著正相关(r_1=0.652,r_2=0.671,P0.05),血清GFAP水平与MMSE分值呈显著负相关(r3=-0.681,P0.05)。结论:血清NGF、BDNF、GFAP水平均与老年血管性痴呆的严重程度密切相关,可能用于评估老年血管性痴呆病情的严重程度。     

p42.3 gene expression in gastric cancer cell and its protein regulatory network analysis

Background

To analyze the p42.3 gene expression in gastric cancer (GC) cell, find the relationship between protein structure and function, establish the regulatory network of p42.3 protein molecule and then to obtain the optimal regulatory pathway.

Methods

The expression of p42.3 gene was analyzed by RT-PCR, Western Blot and other biotechnologies. The relationship between the spatial conformation of p42.3 protein molecule and its function was analyzed using bioinformatics, MATLAB and related knowledge about protein structure and function. Furthermore, based on similarity algorithm of spatial layered spherical coordinate, we compared p42.3 molecule with several similar structured proteins which are known for the function, screened the characteristic nodes related to tumorigenesis and development, and established the multi variable relational model between p42.3 protein expression, cell cycle regulation and biological characteristics in the level of molecular regulatory networks. Finally, the optimal regulatory network was found by using Bayesian network.

Results

(1) The expression amount of p42.3 in G1 and M phase was higher than that in S and G2 phase; (2) The space coordinate systems of different structural domains of p42.3 protein were established in Matlab7.0 software; (3) The optimal pathway of p42.3 gene in protein regulatory network in gastric cancer is Ras protein, Raf-1 protein, MEK, MAPK kinase, MAPK, tubulin, spindle protein, centromere protein and tumor.

Conclusion

It is of vital significance for mechanism research to find out the action pathway of p42.3 in protein regulatory network, since p42.3 protein plays an important role in the generation and development of GC.

     

Activity regulates positive and negative neurotrophin-derived signals to determine axon competition

Developmental axon competition plays a key role in sculpting neural circuitry. Here, we have asked how activity and neurotrophins could interact to select one axon over another. Using compartmented cultures of sympathetic neurons, we show that, in the presence of NGF, local depolarization confers a competitive growth advantage on the depolarized axon collaterals and at the same time disadvantages the growth of unstimulated axons from the same and competing neurons. Depolarization mediates the competitive advantage by activating a CaMKII-MEK pathway, which converges to enhance local NGF-mediated downstream growth signals. Patterned electrical stimulation also acts via this pathway to enhance NGF-promoted axonal growth. In contrast, the competitive disadvantage is due to BDNF secreted from and acting on the unstimulated, competing axons through p75NTR. Thus, activity regulates both positive and negative neurotrophin-derived signaling cascades to confer a competitive growth advantage on one axon versus another, thereby providing a cellular mechanism for developmental axon selection.     

Effects of the neurotrophins nerve growth factor,neurotrophin-3, and brain-derived neurotrophic factor (BDNF) on neurite growth from adult sensory neurons in compartmented cultures

We used compartmented cultures to study the regulation of adult sensory neurite growth by neurotrophins. We examined the effects of the neurotrophins nerve growth factor (NGF), neurotrophin-3 (NT3), and BDNF on distal neurite elongation from adult rat dorsal root ganglion (DRG) neurons. Neurons were plated in the center compartments of three-chambered dishes in the absence of neurotrophin, and neurite extension into the distal (side) compartments containing NGF, BDNF, or NT3 was quantitated. Initial proximal neurite growth did not require any of the neurotrophins, while subsequent elongation into distal compartments required NGF. After neurites had extended into NGF-containing distal compartments, removal of NGF by treatment with anti-NGF resulted in the cessation of growth with minimal neurite retraction. In contrast to the effects of NGF, no distal neurite elongation was observed into compartments with BDNF or NT3. To examine possible additive influences, neurite extension into compartments containing BDNF plus NGF or NT3 plus NGF was quantitated. There was no increased neurite extension into NGF plus NT3 compartments, while the combination of BDNF plus NGF resulted in an inhibition of neurite extension compared with NGF alone. We then investigated whether the regrowth of neurites that had originally grown into NGF subsequent to in vitro axotomy still required NGF. The results demonstrated that unlike adult sensory nerve regeneration in vivo, the in vitro regrowth did require NGF, and neither BDNF nor NT3 was able to substitute for NGF. Since the initial growth from neurons after dissociation (which is also a regenerative response) did not require NGF, it would appear that neuritic growth and regrowth of adult DRG neurons in vitro includes both NGF-independent and NGF-dependent components. The compartmented culture system provides a unique model to further study aspects of this differential regulation of neurite growth. © 1997 John Wiley & Sons, Inc. J Neurobiol 33: 395–410, 1997     

Association between ACE gene polymorphism and carotid stenosisand and construction of related gene regulatory networks

ObjectiveTo investigate the association between DD, ID and II genotypes of ACE gene and carotid stenosis, and to construct a network of ACE-related genes regulating carotid stenosis.ApproachesMeta-analysis was used to study the association between three genotypes DD, ID and II of carotid stenosis susceptibility gene ACE; functional annotation of ACE gene was conducted by GO analysis; and a network of ACE-related genes that regulate the mechanisms of carotid stenosis was established.ResultsMeta-analysis showed that DD and II genotypes of ACE gene were associated with carotid stenosis. GO analysis showed that the main biological processes involved in ACE include: the process of transforming angiotensinogen into mature angiotensin; angiotensin’s mediation of the brain's response to alcohol consumption and thirst control; any chemical reaction involving the regulation of angiotensin; and the process of catalyzing the release of a C-terminal dipeptide from a polypeptide chain. A network of ACE gene regulation of carotid stenosis was constructed in combination with KEGG analysis.ConclusionThe ACE gene is a susceptibility gene for carotid stenosis. Through the functional annotation and pathway analysis of ACE gene, an ACE gene-involved carotid stenosis regulatory mechanisms network was constructed.     

髓腔内固定联合低强度脉冲超声对兔股骨中段骨折愈合作用研究

摘要 目的：针对髓腔内固定联合低强度脉冲超声对兔股骨中段骨折愈合作用进行研究。方法：选择成年兔股骨中段骨折40只,作为本次的研究对象,将其平均分为对照组和观察组。所有兔子,在手术前禁水、禁食,对其右后肢进行备皮,称重、麻醉,对照组实施髓腔内固定治疗,观察组实施髓腔内固定联合低强度脉冲超声治疗。治疗后1、2、3、4周对兔子的骨折部位进行影像学检查确定兔子的骨折线模糊情况,并在各周采集样品进行组织学检查。治疗4周后对骨折愈合情况进行检查。结果：观察组愈合程度I级、II级、II级比例均低于对照组相应比例,差异具有统计学意义（P＜0.05）,观察组IV级、V级比例分别为35.0 %、55.0 %,均高于对照组的5.0 %、5.0 %,差异具有统计学意义（P＜0.05）;观察组兔子的在1 w、2 w、3 w、4 w骨折线模糊程度评分高于对照组相应时间评分,差异具有统计学意义（P＜0.05）。结论：在兔股骨中断骨折治疗中,实施髓腔内固定联合低强度脉冲超声,可以提高骨折的愈合速度,加速骨折修复,整体治疗效果显著,可以在临床上进行推广实施。     

Myelin-associated glycoprotein activation triggers glutamate uptake by oligodendrocytes in vitro and contributes to ameliorate glutamate-mediated toxicity in vivo

BackgroundMyelin-associated glycoprotein (MAG) is a key molecule involved in the nurturing effect of myelin on ensheathed axons. MAG also inhibits axon outgrowth after injury. In preclinical stroke models, administration of a function-blocking anti-MAG monoclonal antibody (mAb) aimed to improve axon regeneration demonstrated reduced lesion volumes and a rapid clinical improvement, suggesting a mechanism of immediate neuroprotection rather than enhanced axon regeneration. In addition, it has been reported that antibody-mediated crosslinking of MAG can protect oligodendrocytes (OLs) against glutamate (Glu) overload by unknown mechanisms.PurposeTo unravel the molecular mechanisms underlying the protective effect of anti-MAG therapy with a focus on neuroprotection against Glu toxicity.ResultsMAG activation (via antibody crosslinking) triggered the clearance of extracellular Glu by its uptake into OLs via high affinity excitatory amino acid transporters. This resulted not only in protection of OLs but also nearby neurons. MAG activation led to a PKC-dependent activation of factor Nrf2 (nuclear-erythroid related factor-2) leading to antioxidant responses including increased mRNA expression of metabolic enzymes from the glutathione biosynthetic pathway and the regulatory chain of cystine/Glu antiporter system xc^? increasing reduced glutathione (GSH), the main antioxidant in cells. The efficacy of early anti-MAG mAb administration was demonstrated in a preclinical model of excitotoxicity induced by intrastriatal Glu administration and extended to a model of Experimental Autoimmune Encephalitis showing axonal damage secondary to demyelination.ConclusionsMAG activation triggers Glu uptake into OLs under conditions of Glu overload and induces a robust protective antioxidant response.     

盐酸美金刚联合银杏叶提取物对阿尔茨海默病患者血清BDNF、NGF、DA水平和认知功能的影响

目的:探讨盐酸美金刚联合银杏叶提取物对阿尔茨海默病患者血清脑源性神经营养因子(BDNF)、神经营养因子(NGF)浓度、多巴胺(DA)水平和认知功能的影响。方法:将我院2017年6月至2018年7月收治的92例阿尔茨海默病患者按随机数字表法分为对照组49例和研究组43例,对照组采用盐酸美金刚治疗,研究组在对照组基础上联合银杏叶提取物治疗。比较两组临床疗效,治疗前后血清BDNF、NGF、DA水平、认知功能、简易精神状态检查量表(MMSE)、日常生活能力(ADL)评分的变化和不良反应的发生情况。结果:治疗后,研究组总有效率为90.70%,显著高于对照组(69.39%,P0.05)。治疗前,两组血清BDNF、NGF、DA水平、MMSE和ADL评分比较差异无统计学意义(P0.05);治疗后,两组以上指标均较治疗前显著上升,且研究组以上指标明显高于对照组(P0.05)。两组不良反应总发生率比较差异无统计学意义(P0.05)。结论:盐酸美金刚联合银杏叶提取物可提高阿尔茨海默病的疗效,改善患者认知功能,可能与增加BDNF、NGF、DA的表达有关。     

Molecular Evolution of Three Avian Neurotrophin Genes: Implications for Proregion Functional Constraints

Neurotrophin proteins are essential for the survival, differentiation, and maintenance of neurons in the peripheral and central nervous systems. Recent studies have shown that the unprocessed proforms of the neurotrophins are preferential high-affinity ligands for p75^NTR and potent inducers of p75^NTR-mediated cell death. Here, we explore differences in the selective constraints acting on the proregions of the three avian neurotrophin genes—NT-3, BDNF, and NGF—in an explicit phylogenetic context. We found a 50-fold difference in levels of constraint as estimated by d _N/d _S ratios, with the NGF proregion showing the lowest degree of constraint and BDNF the highest. These patterns suggest that the high conservation exhibited by the BDNF proregion results from intense functional constraints that are relaxed in NGF and somewhat relaxed in NT-3. The proregion of BDNF is likely to have a function that differentiates it from the corresponding regions of the NGF and NT-3 genes, suggesting that BDNF is the avian neurotrophin most likely to be used both in its precursor and mature forms in vivo.     

Identification of Key Genes and Pathways Involved in the Heterogeneity of Intrinsic Growth Ability Between Neurons After Spinal Cord Injury in Adult Zebrafish

In the adult central nervous system (CNS), axon regeneration is a major hurdle for functional recovery after trauma. The intrinsic growth potential of an injured axon varies widely between neurons. The underlying molecular mechanisms of such heterogeneity are largely unclear. In the present study, the adult zebrafish dataset GSE56842 were downloaded. Differentially expressed genes (DEGs) were sorted and deeply analyzed by bioinformatics methods. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of DEGs were performed with the DAVID. A DEGs-associated protein–protein interaction network was constructed from the STRING database and visualized with Cytoscape software. In total, 621 DEGs were identified. GO analysis showed that the biological processes of DEGs focused mainly on the Notch signaling pathway, cell differentiation and positive regulation of neuron differentiation. The molecular functions mainly included calcium-transporting ATPase activity and calcium ion binding and structural constituents of the cytoskeleton. The cellular components included the plasma membrane, spectrin, and cytoplasmic and membrane-bound vesicles. KEGG pathway analysis showed that these DEGs were mainly involved in the metabolic pathway and Notch signaling pathway, and subnetworks revealed that genes within modules were involved in the metabolic pathway, Wnt signaling pathway, and calcium signaling pathway. This study identified DEG candidate genes and pathways involved in the heterogeneity of the intrinsic growth ability between neurons after spinal cord injury in adult zebrafish, which could facilitate our understanding of the molecular mechanisms underlying axon regeneration, and these candidate genes and pathways could be therapeutic targets for the treatment of CNS injury.

     

Finding pathway-modulating genes from a novel Ontology Fingerprint-derived gene network

To enhance our knowledge regarding biological pathway regulation, we took an integrated approach, using the biomedical literature, ontologies, network analyses and experimental investigation to infer novel genes that could modulate biological pathways. We first constructed a novel gene network via a pairwise comparison of all yeast genes’ Ontology Fingerprints—a set of Gene Ontology terms overrepresented in the PubMed abstracts linked to a gene along with those terms’ corresponding enrichment P-values. The network was further refined using a Bayesian hierarchical model to identify novel genes that could potentially influence the pathway activities. We applied this method to the sphingolipid pathway in yeast and found that many top-ranked genes indeed displayed altered sphingolipid pathway functions, initially measured by their sensitivity to myriocin, an inhibitor of de novo sphingolipid biosynthesis. Further experiments confirmed the modulation of the sphingolipid pathway by one of these genes, PFA4, encoding a palmitoyl transferase. Comparative analysis showed that few of these novel genes could be discovered by other existing methods. Our novel gene network provides a unique and comprehensive resource to study pathway modulations and systems biology in general.     

Mechanisms of axon regeneration: The significance of proteoglycans

BackgroundTherapeutics specific to neural injury have long been anticipated but remain unavailable. Axons in the central nervous system do not readily regenerate after injury, leading to dysfunction of the nervous system. This failure of regeneration is due to both the low intrinsic capacity of axons for regeneration and the various inhibitors emerging upon injury. After many years of concerted efforts, however, these hurdles to axon regeneration have been partially overcome.Scope of reviewThis review summarizes the mechanisms regulating axon regeneration. We highlight proteoglycans, particularly because it has become increasingly clear that these proteins serve as critical regulators for axon regeneration.Major conclusionsStudies on proteoglycans have revealed that glycans not only assist in the modulation of protein functions but also act as main players—e.g., as functional ligands mediating intracellular signaling through specific receptors on the cell surface. By regulating clustering of the receptors, glycans in the proteoglycan moiety, i.e., glycosaminoglycans, promote or inhibit axon regeneration. In addition, proteoglycans are involved in various types of neural plasticity, ranging from synaptic plasticity to experience-dependent plasticity.General significanceAlthough studies on proteins have progressively facilitated our understanding of the nervous system, glycans constitute a new frontier for further research and development in this field. This article is part of a Special Issue entitled Neuro-glycoscience, edited by Kenji Kadomatsu and Hiroshi Kitagawa.     

Nerve growth factor activates brain-derived neurotrophic factor promoter IV via extracellular signal-regulated protein kinase 1/2 in PC12 cells

Brain-derived neurotrophic factor (BDNF) is a neuromodulator of nociceptive responses in the dorsal root ganglia (DRG) and spinal cord. BDNF synthesis increases in response to nerve growth factor (NGF) in trkA-expressing small and medium-sized DRG neurons after inflammation. Previously we demonstrated differential activation of multiple BDNF promoters in the DRG following peripheral nerve injury and inflammation. Using reporter constructs containing individual promoter regions, we investigated the effect of NGF on the multiple BDNF promoters, and the signaling pathway by which NGF activates these promoters in PC12 cells. Although all the promoters were activated 2.4-7.1-fold by NGF treatment, promoter IV gave the greatest induction. The p38 mitogen-activated protein kinase (MAPK) inhibitor, SB203580, phosphatidylinositol 3-kinase (PI-3K) inhibitor, LY294003, protein kinase A (PKA) inhibitor, H89, and protein kinase C (PKC) inhibitor, chelerythrine, had no effect on activation of promoter IV by NGF. However, activation was completely abolished by the MAPK kinase (MEK) inhibitors, U0126 and PD98059. In addition, these inhibitors blocked NGF-induced phosphorylation of extracellular signal-regulated protein kinase (ERK) 1/2. Taken together, these results suggest that the ERK1/2 pathway activates BDNF promoter IV in response to NGF independently of NGF-activated signaling pathways involving PKA and PKC.     

Comparative insights using the molecular homology model of BDNF (Brain derived neurotrophic factor) of Varanus komodoensis and the known NGF (Nerve growth factor) structure of Naja atra

BDNF (Brain derived neurotrophic factor) is a secretion protein and a member of the neurotrophin family of growth factors. Structural and functional characterization of BDNF Varanus komodoensis is of interest while its structure remains unknown. Thus, a homology molecular model of BDNF was constructed for gleaning possible structural insights. The model was compared with the structure of the homologous NGF (Nerve growth factor, another member of neuro-trophin family) from Naja atra. Comparative structural analysis of the models showed structural similarities with their predicted cavities for the interpretation of potential functional analogy.     

Dendrite regeneration in C. elegans is controlled by the RAC GTPase CED-10 and the RhoGEF TIAM-1

Neurons are vulnerable to physical insults, which compromise the integrity of both dendrites and axons. Although several molecular pathways of axon regeneration are identified, our knowledge of dendrite regeneration is limited. To understand the mechanisms of dendrite regeneration, we used the PVD neurons in C. elegans with stereotyped branched dendrites. Using femtosecond laser, we severed the primary dendrites and axon of this neuron. After severing the primary dendrites near the cell body, we observed sprouting of new branches from the proximal site within 6 hours, which regrew further with time in an unstereotyped manner. This was accompanied by reconnection between the proximal and distal dendrites, and fusion among the higher-order branches as reported before. We quantified the regeneration pattern into three aspects–territory length, number of branches, and fusion phenomena. Axonal injury causes a retraction of the severed end followed by a Dual leucine zipper kinase-1 (DLK-1) dependent regrowth from the severed end. We tested the roles of the major axon regeneration signalling hubs such as DLK-1-RPM-1, cAMP elevation, let-7 miRNA, AKT-1, Phosphatidylserine (PS) exposure/PS in dendrite regeneration. We found that neither dendrite regrowth nor fusion was affected by the axon injury pathway molecules. Surprisingly, we found that the RAC GTPase, CED-10 and its upstream GEF, TIAM-1 play a cell-autonomous role in dendrite regeneration. Additionally, the function of CED-10 in epidermal cell is critical for post-dendrotomy fusion phenomena. This work describes a novel regulatory mechanism of dendrite regeneration and provides a framework for understanding the cellular mechanism of dendrite regeneration using PVD neuron as a model system.     

Activation of casein kinase II and inhibition of phosphatase and tensin homologue deleted on chromosome 10 phosphatase by nerve growth factor/p75NTR inhibit glycogen synthase kinase-3beta and stimulate axonal growth

Axonal elongation and guidance are controlled by extracellular factors such as the neurotrophins. Indeed, nerve growth factor (NGF) seems to promote axon growth through binding to its p75NTR receptor and inactivating RhoA. Furthermore, the local inhibition of glycogen synthase kinase (GSK)-3beta by NGF also favors microtubule polymerization and axon extension. Inactivation of GSK-3beta may be due to the NGF/TrkA-mediated activation of phosphatidylinositol-3 kinase (PI-3 kinase), which increases the levels of phosphatydilinositol 3-phosphate [PI3P]. However, we show here that NGF may inactivate GSK-3beta through an alternative mechanism. In cultured hippocampal neurons, the capacity of NGF to promote axon elongation is mostly mediated by p75NTR, and the activation of this pathway leads to the inactivation of GSK-3beta. However, the signaling pathway triggered by NGF/p75NTR acts through casein kinase II (CK2). NGF/p75NTR-activated CK2 phosphorylates the phosphatase and tensin homologue deleted on chromosome 10 (PTEN), thus rendering this phosphatase inactive. Like activation of the PI-3 kinase, PTEN inactivation allows PI3P levels to increase, thus favoring GSK-3beta inactivation and axon outgrowth. This newly disclosed mechanism may help to extend the repertoire of pharmacological agents that activate CK2 or that inhibit PTEN to stimulate axon regeneration after trauma or disease.     

Comprehensive analysis of lncRNA–miRNA–mRNA during proliferative phase of rat liver regeneration

This study aims to reveal the regulatory mechanism of lncRNAs–miRNAs–mRNAs network during the proliferative phase of liver regeneration (LR). High-throughput sequencing technology was performed, and a total of 1,738 differentially expressed lncRNAs (DE lncRNAs), 167 known differentially expressed miRNAs (DE miRNAs), and 2,727 differentially expressed mRNAs were identified. Then, the target DE lncRNAs and DE mRNAs regulated by the same miRNAs were screened and a ceRNA regulatory network containing 32 miRNAs, 107 lncRNAs, and 270 mRNAs was constructed. Insulin signaling pathway, pyrimidine metabolism, axon guidance, carbohydrate digestion and absorption, and pyruvate metabolism were significantly enriched in the network. Through literature review and the regulatory relationship between lncRNAs and miRNAs, nine core lncRNAs were identified, which might play important roles during the proliferative phase of rat LR. This study analyzed lncRNA–miRNA–mRNA regulatory network for the first time during the proliferative phase of rat LR, providing clues for exploring the mechanism of LR and the treatment of liver diseases.