Abstract:
:Recent reports show that B7-H4 is highly expressed in a variety of tumor cells, functions as a negative regulator of T cells and then promotes tumor progression. However, its expression and role in intrahepatic cholangiocarcinoma (ICC) remain unclear. In present study, B7-H4 expression in ICC and peritumoral tissues was determined at the level of mRNA and protein, and its bioactivity in ICC cells was studied after modification of B7-H4 expression. Then, the mechanism related to tumor progression induced by B7-H4 expression in ICC cells was explored. Finally, clinical significance of B7-H4 expression in ICC patients was further analyzed. The results showed that B7-H4 expression in ICC was much higher than that in peritumoral tissues at the level of both mRNA and protein. The high level of B7-H4 in ICC cells induced epithelial-to-mesenchymal transitions and promoted invasion and metastasis of tumor cells through activation of ERK1/2 signaling. The elevated B7-H4 expression was associated with the downregulated Bax, upregulated Bcl-2 expression, and activation of caspase-3. Clinically, high B7-H4 expression in tumor samples was significantly related to malignant phenotype, such as lymph node metastasis, high tumor stage, and poor differentiation. ICC patients with high expression of B7-H4 had shorter overall survival (OS) and disease-free survival. Moreover, the B7-H4 expression was an independent prognostic factor for predicting OS and tumor recurrence of ICC patients after operation. In conclusion, high expression of B7-H4 promotes tumor progression of ICC and may be a novel therapeutic target for ICC patients.
journal_name
Cell Death Disjournal_title
Cell death & diseaseauthors
Xie N,Cai JB,Zhang L,Zhang PF,Shen YH,Yang X,Lu JC,Gao DM,Kang Q,Liu LX,Zhang C,Huang XY,Zou H,Zhang XY,Song ZJ,Sun HX,Fu BM,Ke AW,Shi GMdoi
10.1038/s41419-017-0015-6subject
Has Abstractpub_date
2017-12-13 00:00:00pages
3205issue
12issn
2041-4889pii
10.1038/s41419-017-0015-6journal_volume
8pub_type
杂志文章abstract::Abdominal Aortic aneurysm (AAA) is associated with chronic inflammation, cells apoptosis, and impairment of autophagy. BP-1-102, a novel potent STAT3 inhibitor, has been recently reported to significantly block inflammation-related signaling pathways of JAK2/STAT3 and NF-κB, as well as regulate autophagy. However, its...
journal_title:Cell death & disease
pub_type: 杂志文章
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abstract::An increasing interest in liver cancer stemness arises owing to its aggressive behavior and poor prognosis. CD133, a widely known liver cancer stem cell marker, plays critical roles in the maintenance of liver cancer stemness. Thus, exploring the regulatory mechanism of CD133 expression is significant. In the present ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1712-0
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abstract::Epigenetic alteration of tumor suppression gene is one of the most significant indicators in human esophageal squamous cell carcinoma (ESCC). In this study, we identified a novel ESCC hypermethylation biomarker ZNF132 by integrative computational analysis to comprehensive genome-wide DNA methylation microarray dataset...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-1236-z
更新日期:2018-12-18 00:00:00
abstract::The ubiquitination-proteasome and degradation system is an essential process that regulates protein homeostasis. This system is involved in the regulation of cell proliferation, differentiation and survival, and dysregulations in this system lead to pathologies including cancers. The ubiquitination system is an enzyma...
journal_title:Cell death & disease
pub_type: 杂志文章,评审
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abstract::Cornelia de Lange Syndrome is a severe genetic disorder characterized by malformations affecting multiple systems, with a common feature of severe mental retardation. Genetic variants within four genes (NIPBL (Nipped-B-like), SMC1A, SMC3, and HDAC8) are believed to be responsible for the majority of cases; all these g...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.371
更新日期:2013-10-17 00:00:00
abstract::Homeostatic chemokines, such as CXCL12, can affect neuronal activity by the regulation of inhibitory and excitatory neurotransmission, but the mechanisms involved are still undefined. Our previous studies have shown that CXCL12 protects cortical neurons from excitotoxicity by promoting the function of the gene-repress...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2010.10
更新日期:2010-04-01 00:00:00
abstract::Kidney aging leads to an increased incidence of end-stage renal disease (ESRD) in the elderly, and aging is a complex biological process controlled by signaling pathways and transcription factors. Podocyte senescence plays a central role in injury resulting from kidney aging. Here, we demonstrated the critical role of...
journal_title:Cell death & disease
pub_type: 杂志文章
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abstract::UV irradiation elicits acute inflammation in the skin by increasing proinflammatory cytokine production in keratinocytes. However, the downstream protein target(s) that link UV radiation to the activation of signaling pathways responsible for cytokine expression have not been fully elucidated. In this study, we report...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.550
更新日期:2017-10-26 00:00:00
abstract::Neonatal jaundice is prevalent among newborns and can lead to severe neurological deficits, particularly sensorimotor dysfunction. Previous studies have shown that bilirubin (BIL) enhances the intrinsic excitability of central neurons and this can potentially contribute to their overexcitation, Ca2+ overload, and neur...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1979-1
更新日期:2019-10-10 00:00:00
abstract::Our previous study showed that angiotensin II (Ang II) exposure diminished the interaction between nephrin and c-Abl, then c-Abl mediated SHIP2-Akt pathway in the process of podocyte injury in vivo and vitro. However, the relationship between nephrin and c-Abl was unknown. Recently, various studies showed that nephrin...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-017-0225-y
更新日期:2018-02-07 00:00:00
abstract::Primary liver cancer (PLC) may be mainly classified as the following four types: hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), hepatoblastoma (HB), and combined hepatocellular carcinoma and intrahepatic cholangiocarcinoma (cHCC-ICC). The majority of PLC develops in the background of tumor micr...
journal_title:Cell death & disease
pub_type: 杂志文章,评审
doi:10.1038/s41419-020-2509-x
更新日期:2020-05-04 00:00:00
abstract::Emerging evidence suggests that long noncoding RNA (lncRNA) plays pivotal roles in regulating various biological process in human cancers. Titin-antisense RNA1 (TTN-AS1) has been regarded as a tumor promoting lncRNA in numerous cancers. However, the clinical significance and biological function of TTN-AS1 in lung aden...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1811-y
更新日期:2019-07-30 00:00:00
abstract::Increasing evidence indicates that dysregulation of microRNAs (miRNAs) plays a crucial role in human malignancies. Here, we showed that microRNA-422a (miR-422a) expression was dramatically downregulated in gastric cancer (GC) samples and cell lines compared with normal controls, and that its expression level was inver...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0564-3
更新日期:2018-05-01 00:00:00
abstract::Increasing the sensitivity of glioblastoma cells to radiation is a promising approach to improve survival in patients with glioblastoma multiforme (GBM). This study aims to determine if serine/threonine phosphatase (protein phosphatase 6 (PP6)) is a molecular target for GBM radiosensitization treatment. The GBM orthot...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2011.126
更新日期:2011-12-08 00:00:00
abstract::Cancer cells including glioblastoma have typically evolved multiple mechanisms to escape programmed cell death in order to maintain their survival. Defects in cell death mechanisms not only facilitate tumorigenesis but also ensure resistance to current anticancer therapies. This emphasizes that targeting cell death pa...
journal_title:Cell death & disease
pub_type: 杂志文章,评审
doi:10.1038/s41419-017-0021-8
更新日期:2018-01-25 00:00:00
abstract::The incidence of malignant melanoma has continued to rise during the past decades. However, in the last few years, treatment protocols have significantly been improved thanks to a better understanding of the key oncogenes and signaling pathways involved in its pathogenesis and progression. Anticancer therapy would eit...
journal_title:Cell death & disease
pub_type: 杂志文章,评审
doi:10.1038/s41419-017-0059-7
更新日期:2018-01-25 00:00:00
abstract::During radiologic or nuclear accidents, high-dose ionizing radiation (IR) can cause gastrointestinal syndrome (GIS), a deadly disorder that urgently needs effective therapy. Unfortunately, current treatments based on natural products and antioxidants have shown very limited effects in alleviating deadly GIS. Reserve i...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2715-6
更新日期:2020-07-06 00:00:00
abstract::Effective management of breast cancer depends on early diagnosis and proper monitoring of patients' response to therapy. However, these goals are difficult to achieve because of the lack of sensitive and specific biomarkers for early detection and for disease monitoring. Accumulating evidence in the past several years...
journal_title:Cell death & disease
pub_type: 杂志文章,评审
doi:10.1038/cddis.2017.440
更新日期:2017-09-07 00:00:00
abstract::Long non-coding RNAs (lncRNAs) play a vital role in tumourigenesis, including that of glioma. Small nucleolar RNA host gene 1 (SNHG1) is a relatively novel lncRNA that is involved in the development of multiple human tumours. However, its underlying molecular mechanism in glioma has not been completely clarified. In t...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1698-7
更新日期:2019-06-12 00:00:00
abstract::Nilotinib is a second-generation tyrosine kinase inhibitor, designed to specifically inhibit break-point cluster region (BCR)-Abelson (ABL) and developed to treat chronic myeloid leukemia (CML) in patients showing a resistance to imatinib. We previously demonstrated that nilotinib-induced apoptosis was reduced by stem...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.309
更新日期:2013-10-03 00:00:00
abstract::The DEAD/DEAH box helicase 11 (DDX11) plays vital roles in regulating the initiation of DNA replication. However, its precise function and regulation in hepatocellular carcinoma (HCC) have never been reported yet. In the current study, we found that DDX11 was overexpressed in HCC tissues. High DDX11 expression was pos...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2478-0
更新日期:2020-04-24 00:00:00
abstract::miRNAs have emerged as a pivotal component of gene regulatory networks, mediating cytokines secretion, cell cycle, and differentiation regulation. However, how miRNAs collaborate with transcription factors and downstream effector proteins that determine the fate of ovarian cancer cells remains to be understood, especi...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2501-5
更新日期:2020-05-11 00:00:00
abstract::The identification of specific drug targets guides the development of precise cancer treatments. Compared with oncogenes, tumor suppressor genes have been poorly studied in the treatment of breast cancer. We integrate the microRNA expression array from GEO (Gene Expression Omnibus) and TCGA (The Cancer Genome Atlas) d...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-017-0128-y
更新日期:2018-01-24 00:00:00
abstract::Spermidine, a natural polyamine presented widely in mammalian cells, has been implicated to extend the lifespan of several model organisms by inducing autophagy. However, the effect of spermidine against neuronal damage has not yet been fully determined. In this study, neuronal cell injury was induced by treating PC12...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.161
更新日期:2017-04-06 00:00:00
abstract::The homolog of p53 gene, p63, encodes multiple p63 protein isoforms. TAp63 proteins contain an N-terminal transactivation domain similar to that of p53 and function as tumor suppressors; whereas ΔNp63 isoforms, which lack the intact N-terminal transactivation domain, are associated with human tumorigenesis. Accumulati...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.468
更新日期:2013-12-05 00:00:00
abstract::The glutamate-induced excitotoxicity pathway has been reported in several neurodegenerative diseases. Molecules that inhibit the release of glutamate or cause the overactivation of glutamate receptors can minimize neuronal cell death in these diseases. Osmotin, a homolog of mammalian adiponectin, is a plant protein fr...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.538
更新日期:2014-01-30 00:00:00
abstract::We studied Akt inhibition using SC66 in a NOD-SCID xenograft mouse model and a panel of eight ovarian cancer cell lines. Elevated phospho-Akt levels in cancerous tissue were associated with short progression-free survival and overall survival. Cell sensitivity to SC66 was inversely correlated with phospho-Akt and COL1...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1555-8
更新日期:2019-04-11 00:00:00
abstract::Therapy resistance is a major roadblock in oncology. Exacerbation of molecular dysfunctions typical of cancer cells have proven effective in twisting oncogenic mechanisms to lethal conditions, thus offering new therapeutic avenues for cancer treatment. Here, we demonstrate that selective agonists of Transient Receptor...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-03256-5
更新日期:2020-12-07 00:00:00
abstract::Cockayne syndrome (CS) is a progressive developmental and neurodegenerative disorder resulting in premature death at childhood and cells derived from CS patients display DNA repair and transcriptional defects. CS is caused by mutations in csa and csb genes, and patients with csb mutation are more prevalent. A hallmark...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.228
更新日期:2014-05-29 00:00:00
abstract::Missense mutations in TP53 comprise >75% of all p53 alterations in cancer, resulting in highly stabilized mutant p53 proteins that not only lose their tumor-suppressor activity, but often acquire oncogenic gain-of-functions (GOFs). GOF manifests itself in accelerated tumor onset, increased metastasis, increased drug r...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.80
更新日期:2017-03-09 00:00:00