Cancer is a global health issue with a high mortality rate, and early detection significantly improves patient survival rates. Currently, the primary methods for cancer detection include imaging examination and tissue biopsy. However, due to technical limitations, early detection can result in invasiveness, false positives, and other complications for patients. Therefore, there is an urgent need for new cancer biomarkers to address these challenges and enhance the accuracy and non-invasiveness of detection. With advances in molecular biology, nucleic acid biomarkers have become invaluable for early cancer diagnosis, prognosis assessment, and therapeutic monitoring. Epigenetic biomarkers, such as DNA methylation and non-coding RNA, play a crucial role in tumorigenesis by regulating related gene expression. However, although they offer significant potential for early warning, the complexity of the detection process coupled with tissue specificity makes the interpretation of results challenging. Liquid biopsy, such as circulating tumor DNA (ctDNA), provide a non-invasive method for dynamic tumor monitoring. However, its applicability is limited due to low sensitivity and high cost. Combining these two approaches can help address their individual shortcomings. CtDNA methylation enhances screening specificity, while multimodal strategies are expected to overcome the limitations of single techniques. The purpose of this review is to explore the role of cancer nucleic acid markers in cancer diagnosis and prognosis, examine their molecular mechanisms, and evaluate the advantages and limitations of these markers. Additionally, it will discuss biomarkers related to the tumor microenvironment and immune response, and their interactions with nucleic acids.

Liver regeneration from acute injury is well-studied, and various factors and pathways are known to be involved. Circular RNAs (circRNAs) are emerging as critical regulators in liver pathophysiology, yet their roles in liver regeneration remain unclear. Here, we characterized a circular RNA, circLAMC1, which was highly upregulated in rats after partial hepatectomy (PH). Overexpression of circLAMC1 promoted liver cell proliferation in vitro. Further mechanistic studies revealed that circLAMC1 interacted with the microRNA miR-138-5p, and that miR-138-5p directly targeted Gnai2. While miR-138-5p mimics or Gnai2 knockdown repressed the proliferative effects mediated by circLAMC1, inhibition of miR-138-5p or Gnai2 upregulation enhanced liver cell proliferation. In vivo, AAV9-mediated circLAMC1 overexpression in mice increased the liver/body weight ratio, reduced liver injury, and increased the number of hepatocytes after PH. Furthermore, circLAMC1 activated the ERK signaling pathway through the miR-138-5p/Gnai2 axis, ultimately upregulating cell cycle proteins. Collectively, our data reveal a specific role for circLAMC1 in liver regeneration and provide a potential regulatory target for promoting liver regeneration after injury.

As an inflammatory regulator, intestinal regenerating islet-derived 3 gamma (RegⅢγ) contributes to alleviating liver injury in liver diseases and colitis. However, it is unclear whether hepatic RegⅢγ exerts a vital impact on liver regeneration (LR). In this study, the expression profile and localization of RegⅢγ in LR were demonstrated by microarray analysis, qRT-PCR and immunofluorescence staining. Then, RAW264.7 cells with RegⅢγ deficiency and overexpression were obtained by the CRISPR/Cas9 system and lentivirus infection, respectively. MTT, flow cytometry, EdU, transwell, neutral red phagocytosis, and NO assays were performed to detect the functions of RegⅢγ in RAW264.7 cell proliferation and inflammation. Finally, the regulatory mechanism of RegⅢγ was explored by co-immunoprecipitation and Western blot assays. According to our findings, RegⅢγ showed significant expression changes in Kupffer cells during LR, and RegⅢγ overexpression stimulated the viability, proliferation, phagocytosis and migration of RAW264.7 cells, whereas RegⅢγ deficiency reversed these effects. Similarly, RegⅢγ overexpression facilitated the expression of HO-1 and IL-10, while RegⅢγ deficiency promoted NO production and p-Akt, p-STAT3, p-p65 and TNF-α expression. In conclusion, RegⅢγ may facilitate LR by promoting the proliferation of macrophages and inhibiting their inflammatory response through Akt, STAT3 and NF-κB pathways in the priming stage of LR.

Background Idiopathic pulmonary fibrosis (IPF) is the result of multiple cycles of epithelial cell injury and fibroblast activation; currently, there is no clear etiology. Increasing evidence suggests that protein metabolism and amino acids play a crucial role in IPF, but the role of D-amino acids is not yet clear. The aim of this study was to identify novel mediators in order to test the hypothesis that D-amino acid oxidase (DAO) plays a significant role in the pathogenesis of IPF.Methods We analyzed DAO gene expression in patients with IPF and mice with bleomycin (BLM)-induced lung fibrosis. We performed in vitro and in vivo assays to determine the effect of DAO on primary type II alveolar epithelial cells from mice and A549 cells.Results DAO expression was downregulated in the lungs of IPF patients and BLM-induced fibrotic mice. Treatment with D-serine (D-Ser) or drug inhibition of DAO promoted cell senescence through the p53/p21 pathway. Dao -/- mice showed an intensified fibrotic response, and the anti-fibrotic role of T3 was abolished.Conclusion We concluded that the DAO-p53/p21 axis might be a key anti-fibrotic pathway regulating the progress of fibrosis and facilitating the therapeutic role of T3.

Liver fibrosis represents the reversible pathological process with the feature of the over-accumulation of extracellular matrix (ECM) proteins within the liver, which results in the deposition of fibrotic tissues and liver dysfunction. Circular noncoding RNAs (CircRNAs) have the characteristic closed loop structures, which show high resistance to exonuclease RNase, making them far more stable and recalcitrant against degradation. CircRNAs increase target gene levels by playing the role of a microRNA (miRNA) sponge. Further, they combine with proteins or play the role of RNA scaffolds or translate proteins to modulate different biological processes. Recent studies have indicated that CircRNAs play an important role in the occurrence and progression of liver fibrosis and may be the potential diagnostic and prognostic markers for liver fibrosis. This review summarizes the CircRNAs roles and explores their underlying mechanisms, with a special focus on some of the latest research into key CircRNAs related to regulating liver fibrosis. Results in this work may inspire fruitful research directions and applications of CircRNAs in the management of liver fibrosis. Additionally, our findings lay a critical theoretical foundation for applying CircRNAs in diagnosing and treating liver fibrosis.

Objective To explore the effect of serine protease inhibitor Kazal-type 1(SPINK1)on the proliferation of hepatocellular carcinoma cells RH-35 and its underling molecular mechanism.Methods Spink1 gene expression in liver cancer and rat liver cancer models were analyzed by Gene Expression Omnibus(GEO)data,RH-35 cells were treated with rrSPINK1 protein,the effect of rrSPINK1 on the proliferation and apoptosis of RH-35 cells was explored by MTT,2'-deoxy-5-ethynyluridine(EdU)and flow cytometry,the molecular mechanism of SPINK1 regulating liver cancer were detected by Real-time PCR and Western blotting.Results The results showed that Spink1 gene was over-expressed significantly in liver cancer and rat liver cancer models,rrSPINK1-treated RH-35 cells showed increased viability,EdU-positive cell rate,and the proportion of cells in S phase and G2/M phase compared to the control group.However,there was no significant difference in RH-35 cell apoptosis.rrSPINK1 up-regulated the expression of p38 MAPK and STAT pathway-related genes/proteins in RH-35 cells;and the expression of Spink1 gene in liver cancer was positively correlated with that of Mpak13,Stat1 and Stat3 genes.Conclusion SPINK1 may promote the expression of p38 MAPK and Januk kinase/signal transducers and activators of transcription(JAK/STAT),and promote the proliferation of hepatocellular carcinoma cells.

目的 了解大鼠肝再生(LR)0h和6h时骨髓瘤基因(MYC)及其mRNA相互作用的微小RNA(miRNA,miR)和环状RNA(circRNA)的表达变化、相互作用和调节残肝炎症反应的途径与方式.方法 按Higgins等方法制备大鼠2/3肝切除(PH)模型,用大规模定量检测技术测定大鼠肝再生中残肝的mRNA、miRNA和circRNA[合称内源竞争RNA(ceRNA)]表达变化,用Cytoscape 3.2软件构建ceRNA的相互作用网,用ceRNA综合分析等方法解析它们的表达相关性和作用相关性.结果 PH后0h和6h时,MYCmRNA的比值为0.15±0.03和2.36±0.20,miR-540-3p 为 3.00±0.43 和 0.79±0.01,circRNA_04996 为 1.43±0.43 和 3.14±0.94.同时,PH 后 0 h时,MYC促进的纤溶酶原激活剂尿激酶受体(PLAUR)、肿瘤坏死因子(TNF)、白细胞介素1受体2型(IL1R2)等3个炎症反应相关基因表达下调,抑制的炎症反应相关基因利钠肽A(NPPA)、核受体亚家族0组B成员2(NROB2)和过氧化物酶体增殖物激活受体α(PPARA)表达上调.PH后6 h时,MYC促进的PLAUR、TNF、IL1R2等3个炎症反应相关基因表达上调,抑制的炎症反应相关基因NPPA、NROB2和PPARA表达下调.结论 上述circRNA抑制的miRNA、miRNA抑制的MYC mRNA以及MYC调节的炎症反应相关基因的表达相关性和作用相关性有利于PH后0 h时残肝处于非炎症反应状态和PH后6 h时残肝处于炎症反应状态.

G protein-coupled receptors (GPCRs) play important roles in tumorigenesis and the development of hepatocellular carcinoma (HCC). GPR50 is an orphan GPCR. Previous studies have indicated that GPR50 could protect against breast cancer development and decrease tumor growth in a xenograft mouse model. However, its role in HCC remains indistinct. To detect the role and the regulation mechanism of GPR50 in HCC, GPR50 expression was analyzed in HCC patients (gene expression omnibus database (GEO) (GSE45436)) and detected in HCC cell line CBRH-7919, and the results showed that GPR50 was significantly up-regulated in HCC patients and CBRH-7919 cell line compared to the corresponding normal control. Gpr50 cDNA was transfected into HCC cell line CBRH-7919, and we found that Gpr50 promoted the proliferation, migration, and autophagy of CBRH-7919. The regulation mechanism of GPR50 in HCC was detected by isobaric tags for relative and absolute quantification (iTRAQ) analysis, and we found that GPR50 promoted HCC was closely related to CCT6A and PGK1. Taken together, GPR50 may promote HCC progression via CCT6A-induced proliferation and PGK1-induced migration and autophagy, and GPR50 could be an important target for HCC.

Fat storage-inducing transmembrane proteins (FITMs) were initially identified in 2007 as members of a conserved endoplasmic reticulum (ER) resident transmembrane protein gene family, and were found to be involved in lipid droplet (LD) formation. Recently, several studies have further demonstrated that the ability of FITMs to directly bind to triglyceride and diacylglycerol, and the diphosphatase activity of hydrolyzing fatty acyl-CoA, might enable FITMs to maintain the formation of lipid droplets, engage in lipid metabolism, and protect against cellular stress. Based on the distribution of FITMs in tissues and their important roles in lipid droplet biology and lipid metabolism, it was discovered that FITMs were closely related to muscle development, adipocyte differentiation, and energy metabolism. Accordingly, the abnormal expression of FITMs was not only associated with type 2 diabetes and lipodystrophy, but also with cardiac disease and several types of cancer. This study reviews the structure, distribution, expression regulation, and functionality of FITMs and their potential relationships with various metabolic diseases, hoping to provide inspiration for fruitful research directions and applications of FITM proteins. Moreover, this review will provide an important theoretical basis for the application of FITMs in the diagnosis and treatment of related diseases.

The liver has the powerful capacity to regenerate after injury or resection. In one of our previous studies, GPR50 was observed to be significantly upregulated at 6 h, following a partial hepatectomy (PH) in rat liver regeneration (LR) via gene expression profile. However, little research has been done on the regulation and mechanism of GPR50 in the liver. Herein, we observed that the overexpression of GPR50 inhibited the proliferation of BRL-3A cells. To further explore the molecular mechanisms of GPR50 in the regulation of BRL-3A cell proliferation, interaction between GPR50 and transforming growth factor-beta I (TβRI) and iTRAQTM differential proteomic analysis were elucidated, which suggested that GPR50 may interact with TβRI to activate the TGF-β signaling pathway and arrest BRL-3A cell cycle G1/S transition. Subsequently, the potential mechanism underlying the role of GPR50 in hepatocyte growth was also explored through the addition of a signaling pathway inhibitor. These data suggested that interaction between the orphan GPR50 receptor and TβRI induced the G1⁄S-phase cell cycle arrest of BRL-3A cells via the Smad3-p27/p21 pathway.

OBJECTIVES:As a multifunctional molecule, NO has different effects on liver injury. The present work aimed to investigate the effects of Nos2 knockout (KO) on acute liver injury in aged mice treated with carbon tetrachloride (CCl4).MATERIALS AND METHODS:The acute liver injury model was produced by CCl4 at 10 ml/kg body weight in 24-month-old Nos2 KO mice and wild type (WT) mice groups. The histological changes, transaminase and glutathione (GSH) contents, and the expressions of liver function genes superoxide dismutase (SOD2) and butyrylcholinesterase (BCHE), as well as apoptosis- and inflammation-associated genes were detected at 0, 6, 16, 20, 28, and 48 hr, respectively.RESULTS:Compared with WT aged mice, there are more fat droplets in liver tissues of Nos2 KO aged mice, and the serum levels of ALT and AST were elevated in the KO group; in addition, there was a decrease in the expression of SOD2 and BCHE and GSH content at multiple time-points. Furthermore, the expression of apoptosis protein CASPASE-3 was elevated from 20 to 48 hr, the same as CASPASE-9 at 28 and 48 hr and pro-apoptotic protein BAX at 6 and 28 hr, while the expression of apoptosis inhibitory protein BCL2 declined at 6 and 28 hr; at the same time the mRNA expressions of genes related to inflammation were increased at different extents in liver extracts of Nos2 KO aged mice.CONCLUSION:Nos2 KO exacerbated liver injury probably by elevated oxidative stress, apoptosis and inflammation response in CCl4-induced aged mice liver intoxication model.

Cell proliferation constitutes the fundamental process and driving force behind regrowth during liver regeneration (LR). However, it remains unclear how competing endogenous RNA (ceRNA) networks affect hepatocyte proliferation and liver regeneration. Therefore, this study was designed to explore an LR-specific ceRNA network, which regulates cell proliferation. Based on the microarray data of mRNAs, and high-throughput sequencing data of miRNAs and circRNAs from regenerating livers, this study initially applied known 1484 LR associated mRNAs to perform GO analysis, and then selected 169 LR associated mRNAs involved in cell proliferation and the cell cycle. Subsequently, 188 interactive miRNA–mRNA pairs and 5206 circRNA–miRNA pairs, respectively, were predicted using bioinformatics methods. Next, in view of the differential expressions of these ceRNAs during LR, 26 miRNA–mRNA pairs and 71 circRNA–miRNA pairs were applied to generate a circRNA–miRNA–mRNA regulatory network, and only 14 triple interactive groups were obtained based on the predicted inverse interactions among ceRNAs. Finally, circ_19698/miR-423-5p axis was demonstrated to promote cell proliferation by modulating the expression of MYC, CCNA2, and CCND1 in rat BRL-3A cells. This study suggests a potential regulatory mechanism of cell proliferation in regenerating livers, as well as a novel pathway for modulating ceRNA networks to promote liver regeneration.

The serine protease inhibitor, Kazal type III (SPINK3), is a trypsin inhibitor associated with liver disease, which highly overexpresses in a variety of cancers. In one of our previous studies of our laboratory, Spink3 was observed to be significantly upregulated in rat liver regeneration (LR) via a gene expression profile. For the current study, rat hepatocyte BRL-3A cells were treated by gene addition/interference, and the addition of the exogenous rat recombinant protein SPINK3. It was revealed that both the overexpression of endogenous Spink3 and addition of exogenous rat recombinant SPINK3 (rrSPINK3) significantly promoted the cell proliferation of BRL-3A cells, whereas cell proliferation was inhibited when Spink3 was interfered. Furthermore, quantitative reverse transcription polymerase chain reaction and western blot results revealed that three signaling pathways, including extracellular-signal-regulated kinase 1/2 (ERK1/2), Janus kinase (JAK)-signal transducer and activator of transcription (STAT), and phosphatidylinositol-3-kinase (PI3K)-protein kinase B (AKT), as well as their related genes, were altered following endogenous Spink3 addition/interference. Also, the PI3K-AKT and SRC-p38 pathways and their related genes were modified following exogenous SPINK3 treatment. Among them, the common signaling pathway was PI3K-AKT pathway. We concluded that SPINK3 could activate the PI3K-AKT pathway by enhancing the expression of AKT1 to regulate the proliferation of BRL-3A cells. This study may contribute to shedding light on the potential mechanisms of SPINK3 that regulate the proliferation of BRL-3A cells.

Regenerating islet-derived protein (Reg) could participate in the occurrence of diabetes mellitus, inflammation, tumors, and other diseased or damaged tissues. However, the correlation of Reg with acute hepatic failure (AHF) and hepatocellular carcinoma (HCC) is poorly defined. To reveal the expression profiles of Reg family and their possible regulatory roles in AHF and HCC, rat models of HCC and AHF were separately established, and Rat Genome 230 2.0 was used to detect expression profiles of Reg-mediated signaling pathways-associated genes from liver tissues in AHF and HCC. The results showed that a total of 79 genes were significantly changed. Among these genes, 67 genes were the AHF-specific genes, 45 genes were the HCC-specific genes, and 33 genes were the common genes. Then, K-means clustering classified these genes into 4 clusters based on the gene expression similarity, and DAVID analysis showed that the above altered genes were mainly associated with stress response, inflammatory response, and cell cycle regulation. Thereafter, IPA software was used to analyze potential effects of these genes, and the predicted results suggested that the Reg-mediated JAK/STAT, NF-κB, MAPK (ERK1/2, P38 and JNK), PLC, and PI3K/AKT signaling pathways may account for the activated inflammation and cell proliferation, and the attenuated apoptosis and cell death during the occurrence of AHF and HCC.

Aim: This study aimed to examine the effects of osteopontin (OPN) on hepatocyte growth and liver regeneration (LR). Methods: A recombinant lentivirus expressing OPN and OPN-siRNAs were used to treat BRL-3A cells, while the adenovirus expressing OPN or OPN-targeted shRNA were applied for rat primary hepatocytes. Moreover, rrOPN and OPN-Ab were added to treat BRL-3A. Next, rrOPN was administrated into rat regenerating livers. Then in vitro and in vivo assays were performed to evaluate the biological function of OPN in hepatocyte growth and LR. Results: OPN overexpression facilitated proliferation and viability of BRL-3A cells and primary hepatocytes, while OPN silencing reversed these effects. Similarly, rrOPN stimulated cell cycle progression and viability, but OPN-Ab led to cell cycle arrest and decreased viability. OPN overexpression induced the expression of p-STAT3, p-AKT and CCND1, and OPN siRNA led to reduction of p-AKT and CCND1. Furthermore, rrOPN promoted the expression of p-STAT3 and p-AKT, while OPN-Ab and PI3K/Akt inhibitor LY294002 both inhibited the expressions of p-AKT and Bcl2. Moreover, LR rate, serum IL-6 and TNF-α, Ki-67+ proportion and the phosphorylation of STAT3, AKT and p65 were augmented by rrOPN treatment. Conclusion: OPN promotes hepatocyte proliferation both in vitro and in vivo through STAT3 and AKT signaling pathways.

Objective Patients over 60 years of age have higher mortality and morbidity after major liver resections. Nitric oxide (NO) derived from the catalytic activity of Nos2 plays a beneficial role in liver regeneration (LR) after partial hepatectomy (PH). In this experiment, we evaluated the effect of Nos2 knockout (KO) on LR in aged mice after PH. Materials and Methods In this experimental study, 52 two-year-old Nos2 KO and 46 the same age wild-type (WT) C57BL/6J mice were subjected to 2/3 PH. Liver tissues were collected at 11 time points after PH. Mice survival ratio and liver coefficient (liver-weight/ body-weight) was calculated. Transcript and protein levels were estimated by reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) and Western blot, respectively. Results The aged Nos2 KO mice had lower survival ratio (P=0.039) and liver coefficient (P=0.002) at the termination phase. Nos2 transcript level was obviously increased after PH in WT mice and undetected in the Nos2 KO mice. During LR, the expression at the transcript level of Cyclin D1, Cyclin A2 and Cyclin B1 and protein expression level of proliferation marker Ki67 and proliferation-associated transcription factors JNK1, NF-kB and STAT3 were decreased or delayed. The expression of pro-apoptotic proteins, CASPASE3, CASPASE9 and BAX, was increased in the Nos2 KO mice. Conclusion Decreased survival ratio and impaired LR in aged Nos2 KO mice is probably due to decreased liver cell proliferation and increased liver cell apoptosis.

Regenerating islet-derived protein (Reg) are a group of 16 kD secretory proteins and belong to the C-type lectin superfamily.Reg proteins are multi-functional molecules,which are mainly involved in regulating cell growth and proliferation in pancreas,stomach,intestine and liver,and play an important role in the development and prognosis of digestive diseases and cancers.We reviewed research progress of the complex roles of Reg family in liver diseases and liver regeneration,including Reg family-mediated signaling pathways in digestive diseases,and laid an important theoretical foundation for application of Reg family in the diagnosis,treatment of digestive diseases and promotion of liver regeneration.

Liver disease is one of the major diseases threatening human health nowadays.The liver has a strong ability to regenerate.Therefore,the development of drug target in liver regeneration plays an important role on liver disease prevention and therapy.Previous studies found that serine protease inhibitor Kazal type Ⅲ(SPINK3) was significantly changed in rat liver regeneration by analysis of gene expression profiles.SPINK3 is not only a trypsin inhibitor,but also a growth factor similar to epidermal growth factor (EGF).SPINK3 can bind to epidermal growth factor receptor (EGFR) and promote cell proliferation.In this study,interference of SPINK3 expression was achieved by transfection of adenovirus vectors with either insertion or deletion of SPINK3 into rat primary hepatocytes.Cell viability was detected by CCK8 and cell proliferation was detected by Ki67 immunofluorescence.In addition,cell cycle was detected by PI single staining and cell apoptosis was detected by Annexin V/PI double staining.The results showed that SPINK3 overexpression increased the cell viability of primary rat hepatocytes,promoted cell cycle and inhibited apoptosis of the cells,while knock down of SPINK3 expression reduced the cell viability,inhibited cell cycle and promoted apoptosis of the cells.

Serine peptidase inhibitor Kazal type I (SPINK1) has the similar spatial structure as epidermal growth factor (EGF); EGF can interact with epidermal growth factor receptor (EGFR) to promote proliferation in different cell types. However, whether SPINK1 can interact with EGFR and further regulate the proliferation of hepatocytes in liver regeneration remains largely unknown. In this study, we investigated the role of SPINK1 in a rat liver hepatocyte line of BRL‐3A in vitro. The results showed the upregulation of endogenous Spink1 (gene addition) significantly increased not only the cell viability, cell numbers in S and G2/M phase, but also upregulated the genes/proteins expression related to cell proliferation and anti‐apoptosis in BRL‐3A. In contrast, the cell number in G1 phase and the expression of pro‐apoptosis‐related genes/proteins were significantly decreased. The similar results were observed when the cells were treated with exogenous rat recombinant SPINK1. Immunoblotting suggested SPINK1 can interact with EGFR. By Ingenuity Pathway Analysis software, the SPINK1 signalling pathway was built; the predicted read outs were validated by qRT‐PCR and western blot; and the results showed that p38, ERK, and JNK pathways‐related genes/proteins were involved in the cell proliferation upon the treatment of endogenous Spink1 and exogenous SPINK1. Collectively, SPINK1 can associate with EGFR to promote the expression of cell proliferation‐related and anti‐apoptosis‐related genes/proteins; inhibit the expression of pro‐apoptosis‐related genes/proteins via p38, ERK, and JNK pathways; and consequently promote the proliferation of BRL‐3A cells. For the first time, we demonstrated that SPINK1 can associate with EGFR to promote the proliferation of BRL‐3A cells via p38, ERK, and JNK pathways. This work has direct implications on the underlying mechanism of SPINK1 in regulating hepatocytes proliferation in vivo and liver regeneration after partial hepatectomy.

Liver cirrhosis (LC) is a kind of liver disease which is pathologically characterized by abnormality and necrosis of hepatic cells, proliferation of fibrous tissue, nodular regeneration and pseudolobule formation. To explore the mechanism of LC occurrence at the level of mRNA, Rat Genome 230 2.0 Array was used to detect gene expression profiles of rat fibrotic livers in 3, 6 and 9 weeks after CCl4 treatment in this study. It was found that a total of 305 genes including 153 up-regulated, 150 down-regulated and 2 up/down-regulated genes, were related to LC occurrence. Then, k-means clustering was employed to classify above 305 genes into 5 clusters based on gene expression similarity, and EASE analysis further indicated that the above genes were mainly associated with metabolic process, stress reaction, cell growth and apoptosis/death. Thereafter, ingenuity pathway analysis (IPA) software was used to analyze potential effects of the above-mentioned 305 genes, and the results suggested that lipid metabolism and cell growth were inhibited while cell apoptosis/death was activated, but immune/inflammatory response was first activated and then inhibited. Furthermore, IPA also predicted that several signal pathways “ERK/MAPK Signaling”, “p38 MAPK”, “Endothelin-1 Signaling”, “Growth Hormone Signaling”, “LPS/IL-1-mediated inhibition of RXR function” and “IL-6 Signaling” were involved in regulating the occurrence of liver cirrhosis. It was concluded that 305 genes and 3 kinds of physiological activities were closely related to LC occurrence. Key words: Liver cirrhosis, gene expression profile, systems biology analysis, physiological activity.