Publications by authors named "Xiaochun Xia"

13 Publications

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SRC-3 deficiency protects host from Listeria monocytogenes infection through increasing ROS production and decreasing lymphocyte apoptosis.

Int Immunopharmacol 2021 Apr 12;96:107625. Epub 2021 Apr 12.

Department of Cardiology, The First Affiliated Hospital of Xiamen University, Xiamen, China. Electronic address:

Listeria monocytogenes is the third major cause of death among food poisoning. Our previous studies have demonstrated that steroid receptor coactivator 3 (SRC-3) plays a critical protective role in host defense against extracellular bacterial pathogens such as Escherichia coli and Citrobacter rodentium. However, its role involved in intracellular bacterial pathogen infection remains unclear. Herein, we found that SRC-3 mice are more resistant to L. monocytogenes infection after tail intravenous injection with L. monocytogenes compared with wild-type mice. After infecting with L. monocytogenes, SRC-3 mice exhibited decreased mortality rate, decreased bacterial load, less body weight loss, less proinflammatory cytokines and less severe tissue damage compared with wild-type mice. SRC-3 mice produced more ROS and decreased L. monocytogenes-induced lymphocyte apoptosis. Mechanically, SRC-3 mice displayed decreased expressions of negative regulator of ROS (NRROS) and interferon (IFN)-β and its target genes such as Daxx, Mx1 and TRAIL associated with apoptosis. Taken together, SRC-3 deficiency can protect host from L. monocytogenes infection through increasing ROS production and decreasing lymphocyte apoptosis via affecting the expressions of NRROS and IFN-β.
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http://dx.doi.org/10.1016/j.intimp.2021.107625DOI Listing
April 2021

RAD18 promotes colorectal cancer metastasis by activating the epithelial‑mesenchymal transition pathway.

Oncol Rep 2020 Jul 21;44(1):213-223. Epub 2020 Apr 21.

Department of Radiation Oncology, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, Jiangsu 215001, P.R. China.

RAD18 is an E3 ubiquitin‑protein ligase that has a role in carcinogenesis and tumor progression owing to its involvement in error‑prone replication. Despite its significance, the function of RAD18 has not been fully examined in colorectal cancer (CRC). In the present research, by collecting clinical samples and conducting immunohistochemical staining, we found that RAD18 expression was significantly increased in the CRC tissue compared with that noted in the adjacent non‑cancerous normal tissues and that high expression of RAD18 was associated with lymph node metastasis and poor prognosis in CRC patients. In vitro, as determined by cell transfection, scratch, and Transwell experiments, it was also demonstrated that RAD18 increased the invasiveness and migration capacity of CRC cells (HCT116, DLD‑1, SW480). The signaling pathway was analyzed by western blotting and the clinical data were analyzed by immunohistochemical staining and RT‑PCR, indicating that the process of epithelial‑mesenchymal transition (EMT) may be involved in RAD18‑mediated migration and invasion of CRC cells. All of the above data indicate that RAD18 is a novel prognostic biomarker that may become a potential therapeutic target for CRC in the future.
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http://dx.doi.org/10.3892/or.2020.7590DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7251712PMC
July 2020

MEIS2C and MEIS2D promote tumor progression via Wnt/β-catenin and hippo/YAP signaling in hepatocellular carcinoma.

J Exp Clin Cancer Res 2019 Oct 17;38(1):417. Epub 2019 Oct 17.

The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, 28, Xianning West Road, Xi'an, 710049, Shaanxi, People's Republic of China.

Background: MEIS2 has been identified as one of the key transcription factors in the gene regulatory network in the development and pathogenesis of human cancers. Our study aims to identify the regulatory mechanisms of MEIS2 in hepatocellular carcinoma (HCC), which could be targeted to develop new therapeutic strategies.

Methods: The variation of MEIS2 levels were assayed in a cohort of HCC patients. The proliferation, clone-formation, migration, and invasion abilities of HCC cells were measured to analyze the effects of MEIS2C and MEIS2D (MEIS2C/D) knockdown with small hairpin RNAs in vitro and in vivo. Chromatin immunoprecipitation (ChIP) was performed to identify MEIS2 binding site. Immunoprecipitation and immunofluorescence assays were employed to detect proteins regulated by MEIS2.

Results: The expression of MEIS2C/D was increased in the HCC specimens when compared with the adjacent noncancerous liver (ANL) tissues. Moreover, MEIS2C/D expression negatively correlated with the prognosis of HCC patients. On the other hand, knockdown of MEIS2C/D could inhibit proliferation and diminish migration and invasion of hepatoma cells in vitro and in vivo. Mechanistically, MESI2C activated Wnt/β-catenin pathway in cooperation with Parafibromin (CDC73), while MEIS2D suppressed Hippo pathway by promoting YAP nuclear translocation via miR-1307-3p/LATS1 axis. Notably, CDC73 could directly either interact with MEIS2C/β-catenin or MEIS2D/YAP complex, depending on its tyrosine-phosphorylation status.

Conclusions: Our studies indicate that MEISC/D promote HCC development via Wnt/β-catenin and Hippo/YAP signaling pathways, highlighting the complex molecular network of MEIS2C/D in HCC pathogenesis. These results suggest that MEISC/D may serve as a potential novel therapeutic target for HCC.
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http://dx.doi.org/10.1186/s13046-019-1417-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6796342PMC
October 2019

Steroid receptor coactivator 3 inhibits hepatitis B virus gene expression through activating Akt signaling to prevent HNF4α nuclear translocation.

Cell Biosci 2019 13;9:64. Epub 2019 Aug 13.

1Department of Hepatobiliary and Pancreatic & Organ Transplantation Surgery, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361012 Fujian China.

Background: Chronic hepatitis B virus (HBV) infection is one of the most serious global public health problems. The role of steroid receptor coactivator 3 (SRC-3) in HBV biosynthesis is unknown. The aim of this study is to investigate the function of SRC-3 in regulating HBV biosynthesis both in vitro and in vivo and to identify the underlying mechanism.

Results: In this study, we found that knockdown of SRC-3 could increase the levels of HBV mRNA and HBV proteins HBsAg and HBeAg in human liver cancer cell line HepG2 transfected with pHBV1.3 plasmids. In contrast, enforced expression of SRC-3 in SRC-3-knockdown HepG2 cells reduced the levels of HBV mRNA and HBV proteins HBsAg and HBeAg. Knockdown of SRC-3 dampened the Akt signaling, which has been shown to play a negative role in HBV transcription. Ectopic expression of constitutively activated Akt impaired the enhancement of HBV transcription by SRC-3 knockdown, indicating that SRC-3 inhibits HBV transcription by enhancing Akt signaling. Both SRC-3 and constitutively activated Akt could inhibit hepatocyte nuclear factor 4α (HNF4α)-mediated upregulation of HBV core promoter activity by preventing HNF4α nuclear translocation. Consistent with the in vitro results, in an in vivo chronic HBV replication mouse model developed by hydrodynamic injection of pHBV1.3 plasmids into mouse tail vein, enforced expression of SRC-3 in mouse liver reduced the levels of HBV mRNA in the liver and HBV antigens in serum, whereas knockout of SRC-3 in mouse increased the levels of HBV mRNA in the liver and HBV antigens in the serum.

Conclusion: Our study suggests that SRC-3 inhibits HBV gene expression by activating Akt signaling to prevent HNF4α nuclear translocation.
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http://dx.doi.org/10.1186/s13578-019-0328-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6692928PMC
August 2019

SRC-3 protects intestine from DSS-induced colitis by inhibiting inflammation and promoting goblet cell differentiation through enhancement of KLF4 expression.

Int J Biol Sci 2018 3;14(14):2051-2064. Epub 2018 Nov 3.

State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiamen, China.

Goblet cell loss, which leads to the reduction of mucin secretion, is a hallmark of ulcerative colitis (UC). We previously reported that steroid receptor coactivator 3 (SRC-3), a transcriptional coactivator, contributes to host defense against by recruiting neutrophils, suggesting a role of SRC-3 in intestine homeostasis. However, the biological role of SRC-3 in UC remains unclear. Here, we showed that SRC-3 mice were more susceptible to dextran sulfate sodium (DSS)-induced colitis compared with wild-type mice after oral administration of 2% DSS dissolved in drinking water. After oral administration of 2% DSS, SRC-3 mice displayed higher mortality rate, significant body weight loss, and higher clinical symptom scores compared to wild-type mice. SRC-3 mice suffered a severe loss of mature colonic goblet cells, leading to more severe histopathology and more proinflammatory cytokine production. Mechanistically, SRC-3 mice exhibited a decreased expression of transcription factor KLF4 in the colons, which is responsible for colonic goblet cell differentiation and maturation. At the molecular level, SRC-3 cooperated with c-Fos to promote KLF4 expression at the transcriptional level. These results demonstrate that SRC-3 can ameliorate DSS-induced colitis by inhibiting inflammation and promoting colonic goblet cell differentiation and maturation through enhancing the expression of transcriptional factor KLF4, which is responsible for colonic goblet cell differentiation and maturation.
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http://dx.doi.org/10.7150/ijbs.28576DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6299374PMC
September 2019

Microtubule-Associated Protein 4 Is a Prognostic Factor and Promotes Tumor Progression in Lung Adenocarcinoma.

Dis Markers 2018 18;2018:8956072. Epub 2018 Mar 18.

Department of Radiation Oncology, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, Jiangsu 215001, China.

Microtubule-associated protein 4 (MAP4) plays an important role in microtubule assembly and stabilization. The purpose of this study was to investigate the level of expression of MAP4 in lung adenocarcinoma (LADC) samples and to evaluate its prognostic value and the influence on cancer progression in LADC patients. The expression of MAP4 protein was analyzed using immunohistochemistry. The clinical significance and the prognostic significance of MAP4 expression were assessed by Kaplan-Meier analysis and Cox regression analysis. The roles of MAP4 in the migration and invasion of LADC cells were detected by wound-healing assays and transwell assays, respectively. We found the expression levels of MAP4 protein in LADC tissues to be significantly higher than those in noncancerous tissues. MAP4 expression was significantly correlated with differentiation, pathological T stage, and TNM stage. Kaplan-Meier survival analysis indicated that patients with high MAP4 expression had significantly poorer overall survival (OS). Cox regression analysis revealed that MAP4 expression level was an independent prognostic factor for OS. Functionally, in vitro studies showed that MAP4 knockdown efficiently suppressed the migration and invasion of LADC cells. Our data indicated that MAP4 protein may represent a novel prognostic biomarker and a potential therapeutic target for LADC.
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http://dx.doi.org/10.1155/2018/8956072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5878896PMC
September 2018

Inhibitory effects of Mycoepoxydiene on macrophage foam cell formation and atherosclerosis in ApoE-deficient mice.

Cell Biosci 2015 26;5:23. Epub 2015 May 26.

State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiang-An South Road, Xiamen, Fujian 360112 China.

Background: Mycoepoxydiene (MED) is a polyketide that can be isolated from a marine fungus and is associated with various activities, including antitumor and anti-inflammatory functions. However, its effects on atherosclerosis remain unknown. Macrophage-derived foam cells play crucial roles in the initiation and progression of atherosclerotic plaques. In this study, we investigated the effects of MED on oxidized low-density lipoprotein (ox-LDL)-induced macrophage foam cell formation and activation, and on high fat diet (HFD)-induced atherosclerosis in ApoE-deficient (ApoE (-/-) ) mice.

Results: Our findings show that MED could significantly inhibit ox-LDL-induced macrophage foam cell formation and suppress the expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), which is a receptor for ox-LDL. Additionally, MED could significantly inhibit the secretion of proinflammatory cytokines, such as tumor necrosis factor (TNF-α), interleukin (IL)-6, and IL-1β. Mechanistically, MED inhibited NF-κB activation by blocking IκB-α degradation and reducing NF-κB DNA binding activity. Moreover, MED dramatically reduced the occurrence of HFD-induced atherosclerotic lesions in ApoE (-/-) mice.

Conclusions: Our study shows that MED can inhibit macrophage foam cell formation and activation by inhibiting NF-κB activation, thereby protecting ApoE (-/-) mice from HFD-induced atherosclerosis. Our findings suggest that MED might be a potential lead compound for the development of antiatherosclerotic therapeutics.
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http://dx.doi.org/10.1186/s13578-015-0017-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4455339PMC
June 2015

Radioprotector WR-2721 and mitigating peptidoglycan synergistically promote mouse survival through the amelioration of intestinal and bone marrow damage.

J Radiat Res 2015 Mar 23;56(2):278-86. Epub 2015 Jan 23.

School of Radiation Medicine and Protection, Soochow University, No. 199 Ren'ai Road, Suzhou 215123, PR China Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, PR China

The identification of an agent effective for the treatment of intestinal and bone marrow injury following radiation exposure remains a major issue in radiological medicine. In this study, we evaluated the therapeutic impact of single agent or combination treatments with 2-(3-aminopropylamino) ethylsulphanyl phosphonic acid (WR-2721) and peptidoglycan (PGN, a toll-like receptor 2 (TLR-2) agonist) on radiation-induced injury of the intestine and bone marrow in lethally irradiated male C57BL/6 mice. A dose of 3 mg of WR-2721 per mouse (167 mg/kg, intraperitoneally) was given 30 min before irradiation, and 30 μg of PGN per mouse (1.7 mg/kg) was injected intraperitoneally 24 h after 10 Gy irradiation. Bone marrow cluster of differentiation (CD)45(+) and CD34(+) markers of multiple haematopoietic lineages, number of granulocyte-erythroid-macrophage-megakaryocyte (GEMM) progenitor colonies, bone marrow histopathology, leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) expression in the intestines, xylose absorption and intestinal histopathology were all assessed at various time-points after irradiation. Furthermore, nuclear factor kappa B (NF-κB) p65 protein in the ileum was stained by immunofluorescent labelling. PGN-treated irradiated mice showed an increase in CD45(+)CD34(+) cells compared with untreated mice 1.25 days after 10 Gy ionizing radiation (IR) (P < 0.05). Furthermore, combined PGN and WR-2721 treatment had an obviously synergistic radio-protective effect in nucleated cells in the bone marrow, including GEMM progenitors and CD45(+)CD34(+) cells 4 days after 10 Gy IR. Single agent PGN or WR-2721 treatment after 10 Gy IR clearly increased Lgr5-positive pit cells (P < 0.05) and xylose absorption (P < 0.05). However only PGN and WR-2721 combination treatment markedly increased villus height (P < 0.05), number of crypts (P < 0.05) and whole-body weights after 10 Gy whole-body irradiation (WBI). The NF-κB p65 subunit was translocated to the nucleus, and phosphate-IκBα (Ser32/Ser36) was detected after stimulation with either PGN or WR-2721, which indicates that these two agents act synergistically through the activation of the NF-κB pathway. Administration of PGN in combination with WR-2721 was demonstrated to have a synergistic effect on the increase in haematopoietic cells and intestinal reconstitution, as well as improved survival in lethally irradiated mice, but resulted in some degree of an immune disorder.
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http://dx.doi.org/10.1093/jrr/rru100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4380048PMC
March 2015

Apoptosis, necrosis, and autophagy in mouse intestinal damage after 15-Gy whole body irradiation.

Cell Biochem Funct 2014 Dec 7;32(8):647-56. Epub 2014 Oct 7.

School of Radiation Medicine and Protection, Soochow University, Suzhou, China; Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, China.

Enterocytes die during high-dose radiation exposure in radiation accidents. The modality of cell death has a profound effect on the therapeutic response. The ilea from mice with 15 Gy total body irradiation (TBI) were drawn, morphological features observed by hematoxylin and eosin staining and transmission electron micrographs. The biochemical features of mouse ileum presented with the structure were cleaved Caspase-3 (apoptosis marker), Light Chain 3 (LC3)-I's conversion to LC3-II (autophagy marker) and high mobility group box chromosomal protein 1's secretion (necrosis marker). Then, the autophagy inhibitor (3-methyladenine), caspase inhibitor (Z-VAD-FMK) or necrosis inhibitor (necrostatin) was used to prevent death. Apoptosis, autophagy and necrosis were all appeared in the ileum, but necrosis had the biggest size; the use of 3-methyladenine and Z-VAD-FMK prolong one day's life of the mice after 15 Gy TBI, necrostatin significantly extended the lifespan of 15 Gy irradiated mice (p < 0.05). The results suggest that the death of enterocytes could not be classified into one type of cell death but rather as 'mixed death.'
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http://dx.doi.org/10.1002/cbf.3068DOI Listing
December 2014

Deficiency in steroid receptor coactivator 3 enhances cytokine production in IgE-stimulated mast cells and passive systemic anaphylaxis in mice.

Cell Biosci 2014 23;4:21. Epub 2014 Apr 23.

State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiang-An South Road, Xiamen, Fujian 360112, China.

Background: Steroid receptor coactivator 3 (SRC-3) is a multifunctional protein that plays an important role in malignancy of several cancers and in regulation of bacterial LPS-induced inflammation. However, the involvement of SRC-3 in allergic response remains unclear. Herein we used passive systemic anaphylaxis (PSA) and passive cutaneous anaphylaxis (PCA) mouse models to assess the role of SRC-3 in allergic response.

Results: SRC-3-deficient mice exhibited more severe allergic response as demonstrated by a significant drop in body temperature and a delayed recovery period compared to wild-type mice in PSA mouse model, whereas no significant difference was observed between two kinds of mice in PCA mouse models. Mast cells play a pivotal role in IgE-mediated allergic response. Antigen-induced aggregation of IgE receptor (FcϵRI) on the surface of mast cell activates a cascade of signaling events leading to the degranulation and cytokine production in mast cells. SRC-3-deficient bone marrow derived mast cells (BMMCs) developed normally but secreted more proinflammatory cytokines such as TNF-α and IL-6 than wild-type cells after antigen stimulation, whereas there was no significant difference in degranulation between two kinds of mast cells. Further studies showed that SRC-3 inhibited the activation of nuclear factor NF-κB pathway and MAPKs including extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase (JNK), and p38 in antigen-stimulated mast cells.

Conclusions: Our data demonstrate that SRC-3 suppresses cytokine production in antigen-stimulated mast cells as well as PSA in mice at least in part through inhibiting NF-κB and MAPK signaling pathways. Therefore, SRC-3 plays a protective role in PSA and it may become a drug target for anaphylactic diseases.
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http://dx.doi.org/10.1186/2045-3701-4-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4021842PMC
May 2014

Prognostic role of microRNA-21 in colorectal cancer: a meta-analysis.

PLoS One 2013 12;8(11):e80426. Epub 2013 Nov 12.

Department of Radiation Oncology, Nantong Tumor Hospital, Nantong, Jiangsu, China.

Background: To date, many studies have shown that microRNAs (miRNA) exhibit altered expression in various cancers and may play an important role as prognostic biomarker of cancers. The present meta-analysis summarizes the recent advances in the use of microRNA-21 (miR-21) in the assessment of colorectal cancer and analyzes the prognostic role of miR-21 for survival outcome.

Methodology/principal Findings: The present meta-analysis was performed by searching PubMed through multiple search strategies. Data were extracted from studies comparing overall survival (OS) in patients with colorectal cancer who showed higher expression of miR-21 than similar patients. Pooled hazard ratios (HRs) of miR-21 for survival and 95% confidence intervals (CI) were calculated. Seven studies with a total of 1174 patients were included this meta-analysis. For overall survival (OS), the pooled hazard ratio (HR) of higher miR-21 expression in colorectal cancer was 1.76 (95% CI: 1.34-2.32, P=0.000). After elimination of heterogeneity, the pooled HR was 2.32 (95% CI: 1.82-2.97, P=0.000), which was found to significantly predict poorer survival. The subgroup analysis suggested that elevated miR-21 level and patients' survival correlated with III/IV stage (HR=5.35, 95% CI: 3.73-7.66).

Conclusions/significance: The present findings suggest that high expression of miR-21 might predict poor prognosis in patients with colorectal cancer.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0080426PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3827229PMC
July 2014

Mycoepoxydiene suppresses RANKL-induced osteoclast differentiation and reduces ovariectomy-induced bone loss in mice.

Appl Microbiol Biotechnol 2013 Jan 9;97(2):767-74. Epub 2012 Jun 9.

State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, China.

Mycoepoxydiene (MED) is a compound isolated from the marine fungal Diaporthe sp. HLY-1 associated with mangroves. MED has various biological effects such as anti-microbial, anti-cancer, and anti-inflammatory activities. However, the effect of MED on the differentiation of osteoclasts, the multinucleated bone-resorbing cells which play a crucial role in bone remodeling, is still unknown. In this study, we showed that MED could inhibit receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation and the expression of three well-known osteoclast markers such as tartrate-resistant acid phosphatase, calcitonin receptor, and cathepsin K in bone marrow-derived macrophages. Furthermore, we found that MED inhibited the expression of nuclear factor of activated T cells c1, a key transcriptional factor in osteoclast differentiation, via inhibiting the phosphorylation of TAK1 and then blocking the activation of NF-κB and ERK1/2 pathways. Moreover, MED could prevent bone loss in ovariectomized mice. Taken together, we demonstrate for the first time that MED can suppress RANKL-induced osteoclast differentiation in vitro and ovariectomy-induced osteoporosis in vivo, suggesting that MED is a potential lead compound for the development of novel drugs for osteoporosis treatment.
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http://dx.doi.org/10.1007/s00253-012-4146-5DOI Listing
January 2013

Amplified in breast cancer 1 enhances human cholangiocarcinoma growth and chemoresistance by simultaneous activation of Akt and Nrf2 pathways.

Hepatology 2012 Jun 25;55(6):1820-9. Epub 2012 Apr 25.

Department of Hepatobiliary Pancreas and Vessel Surgery, Chenggong Hospital of Xiamen University, Xiamen, China.

Unlabelled: Transcriptional coactivator amplified in breast cancer 1 (AIB1) plays important roles in the progression of several cancers such as prostate cancer, breast cancer, and hepatocellular carcinoma. However, its role in cholangiocarcinoma (CCA), a chemoresistant bile duct carcinoma with a poor prognosis, remains unclear. In this study we found that AIB1 protein was frequently overexpressed in human CCA specimens and CCA cell lines. Down-regulation of AIB1 induced the G2/M arrest and decreased the expression of mitosis-promoting factors including Cyclin A, Cyclin B, and Cdk1 through suppressing the Akt pathway, which resulted in inhibiting CCA cell proliferation. In addition, AIB1 enhanced the chemoresistance of CCA cells at least in part through up-regulating the expression of antiapoptotic protein Bcl-2. AIB1 regulated the expression of Bcl-2 in CCA cells through activating the Akt pathway as well as suppressing intracellular reactive oxygen species (ROS). AIB1 suppressed ROS by up-regulating antioxidants such as glutathione synthetase and glutathione peroxidase, which are targets of the NF-E2-related factor 2 (Nrf2), a critical transcription factor that regulates antioxidants, detoxification enzymes, and drug efflux proteins. AIB1 also increased the expression of another two Nrf2 targets, ABCC2 and ABCG2, to enhance drug efflux. AIB1 served as an essential coactivator for Nrf2 activation by physically interacting with Nrf2 to enhance its transcriptional activity.

Conclusion: AIB1 plays an important role in proliferation and chemoresistance of CCA through simultaneous activation of Akt and Nrf2 pathways, suggesting that AIB1 is a potential molecular target for CCA treatment.
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http://dx.doi.org/10.1002/hep.25549DOI Listing
June 2012