Abstract:
:Non-small cell lung cancer (NSCLC) is the leading cause of cancer mortality worldwide. The mechanisms underlying NSCLC tumorigenesis are incompletely understood. Transfer RNA (tRNA) modification is emerging as a novel regulatory mechanism for carcinogenesis. However, the role of tRNA modification in NSCLC remains obscure. In this study, HPLC/MS assay was used to quantify tRNA modification levels in NSCLC tissues and cells. tRNA-modifying enzyme genes were identified by comparative genomics and validated by qRT-PCR analysis. The biological functions of tRNA-modifying gene in NSCLC were investigated in vitro and in vivo. The mechanisms of tRNA-modifying gene in NSCLC were explored by RNA-seq, qRT-PCR, and rescue assays. The results showed that a total of 18 types of tRNA modifications and up to seven tRNA-modifying genes were significantly downregulated in NSCLC tumor tissues compared with that in normal tissues, with the 2'-O-methyladenosine (Am) modification displaying the lowest level in tumor tissues. Loss- and gain-of-function assays revealed that the amount of Am in tRNAs was significantly associated with expression levels of FTSJ1, which was also downregulated in NSCLC tissues and cells. Upregulation of FTSJ1 inhibited proliferation, migration, and promoted apoptosis of NSCLC cells in vitro. Silencing of FTSJ1 resulted in the opposite effects. In vivo assay confirmed that overexpression of FTSJ1 significantly suppressed the growth of NSCLC cells. Mechanistically, overexpression of FTSJ1 led to a decreased expression of DRAM1. Whereas knockdown of FTSJ1 resulted in an increased expression of DRAM1. Furthermore, silencing of DRAM1 substantially augmented the antitumor effect of FTSJ1 on NSCLC cells. Our findings suggested an important mechanism of tRNA modifications in NSCLC and demonstrated novel roles of FTSJ1 as both tRNA Am modifier and tumor suppressor in NSCLC.
journal_name
Cell Death Disjournal_title
Cell death & diseaseauthors
He Q,Yang L,Gao K,Ding P,Chen Q,Xiong J,Yang W,Song Y,Wang L,Wang Y,Ling L,Wu W,Yan J,Zou P,Chen Y,Zhai Rdoi
10.1038/s41419-020-2525-xsubject
Has Abstractpub_date
2020-05-11 00:00:00pages
348issue
5issn
2041-4889pii
10.1038/s41419-020-2525-xjournal_volume
11pub_type
杂志文章abstract::Cancer-initiating cell (CIC) is critical in cancer development, maintenance and recurrence. The reverse expression pattern of coxsackie and adenovirus receptor (CAR) and αν integrin in bladder cancer decreases the infection efficiency of adenovirus. We constructed Arg-Gly-Asp (RGD)-modified oncolytic adenovirus, carry...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2015.128
更新日期:2015-05-14 00:00:00
abstract::Inhibitor of Apoptosis Proteins act as E3 ubiquitin ligases to regulate NF-κB signalling from multiple pattern recognition receptors including NOD2, as well as TNF Receptor Superfamily members. Loss of XIAP in humans causes X-linked Lymphoproliferative disease type 2 (XLP-2) and is often associated with Crohn's diseas...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0508-y
更新日期:2018-05-01 00:00:00
abstract::Tumor-associated thrombosis is the second leading risk factor for cancer patient death, and platelets activity is abnormal in cancer patients. Discovering the mechanism of platelet activation and providing effective targets for therapy are urgently needed. Cancer cell- derived IgG has been reported to regulate develop...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1367-x
更新日期:2019-01-28 00:00:00
abstract::The development of nephrotoxicity largely limits the clinical use of chemotherapy. MiRNAs are able to target various genes and involved in the regulation of diverse cellular processes, including cell apoptosis and death. Our study showed that miR-181a expression was significantly increased after 5-fluorouracil (5-FU) ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0677-8
更新日期:2018-05-23 00:00:00
abstract::Withanolide E, a steroidal lactone from Physalis peruviana, was found to be highly active for sensitizing renal carcinoma cells and a number of other human cancer cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis. Withanolide E, the most potent and least toxic of five TRAIL-se...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2015.38
更新日期:2015-02-26 00:00:00
abstract::Gastric cancer (GC) is one of the most leading malignancies. Long noncoding RNA is related to GC. In this study, 11 miRNAs in the exosomes and six lncRNAs in the tissues was examined by qRT-PCR. Correlation analysis was used to analyze the relationship between miRNAs in exosome and lncRNAs in the tissues. Four miRNAs ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-02946-4
更新日期:2020-09-19 00:00:00
abstract::As a common female malignancy, triple-negative breast cancer (TNBC) is the most serious subtype in breast cancer (BC). BAALC binder of MAP3K1 and KLF4 (BAALC) is a common oncogene in acute myelocytic leukemia (AML). We sought to explore the role of BAALC in TNBC. In this study, BAALC was significantly upregulated in T...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-02821-2
更新日期:2020-08-18 00:00:00
abstract::Despite the introduction of novel targeted therapies, chemotherapy still remains the primary treatment for metastatic melanoma in poorly funded healthcare environments or in case of disease relapse, with no reliable molecular markers for progression-free survival (PFS) available. As chemotherapy primarily eliminates c...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2309-3
更新日期:2020-02-13 00:00:00
abstract::Mammalian target of rapamycin (mTOR) is involved in insulin resistance (IR) and diabetic retinopathy. In retinal pigment epithelial (RPE) cells, insulin activates the mTOR pathway, inducing hypoxia-inducible factor-1α (HIF-1α) and HIF-dependent transcription in serum-free minimum essential medium Eagle (MEM). Serendip...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.178
更新日期:2014-05-08 00:00:00
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::Japanese encephalitis (JE) caused by Japanese encephalitis virus (JEV) poses a serious threat to the world's public health yet without a cure. Certain JEV-infected neural cells express a subset of previously identified intrinsic antiviral interferon stimulated genes (ISGs), indicating brain cells retain autonomous ant...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0763-y
更新日期:2018-06-18 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::Sponges of the porifera family harbor some of the evolutionary most ancient orthologs of the B-cell lymphoma-2 (Bcl-2) family, a protein family critical to regulation of apoptosis. The genome of the sponge Geodia cydonium contains the putative pro-survival Bcl-2 homolog BHP2, which protects sponge tissue as well as ma...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2016.469
更新日期:2017-01-12 00:00:00
abstract::Hedgehog (Hh) inhibitors have emerged as valid tools in the treatment of a wide range of cancers. Indeed, aberrant activation of the Hh pathway occurring either by ligand-dependent or -independent mechanisms is a key driver in tumorigenesis. The smoothened (Smo) receptor is one of the main upstream transducers of the ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2016.195
更新日期:2016-09-22 00:00:00
abstract::Reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress are paradoxically implicated in myocardial ischemia/reperfusion (I/R) injury and cardioprotection. However, the precise interpretation for the dual roles of ROS and its relationship with the ER stress during I/R remain elusive. Here we investigated th...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.267
更新日期:2014-06-19 00:00:00
abstract::Cervical cancer is the most common gynecological malignancy in the world; however, the survival rates of advanced-stage and recurrent cervical cancer patients remain poor. The multifaced protein insulin-like growth factor 2 receptor (IGF2R) has various ligands, represented as IGF-2 and mannose-6-phosphate (M6P)-tagged...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-2117-9
更新日期:2019-11-20 00:00:00
abstract::MicroRNAs have emerged as important post-transcriptional regulators of gene expression and are involved in diverse diseases and cellular process. Decreased expression of miR-181a has been observed in the patients with coronary artery disease, but its function and mechanism in atherogenesis is not clear. This study was...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1599-9
更新日期:2019-05-07 00:00:00
abstract::Holliday junction recognition protein (HJURP) refers to a histone H3 chaperone that has been implicated in different kinds of malignancies. Yet, its character in pancreatic cancer remains unclear. The expression of HJURP was assessed in PDAC tissues by RT-qPCR, immunoblotting, and immunohistochemistry. HJURP-deficient...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2595-9
更新日期:2020-05-21 00:00:00
abstract::Tumor metastasis leads to high mortality; therefore, understanding the mechanisms that underlie tumor metastasis is crucial. Generally seen as a secretory protein, osteopontin (OPN) is involved in multifarious pathophysiological events. Here, we present a novel pro-metastatic role of OPN during metastatic colonization...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2016.422
更新日期:2016-12-29 00:00:00
abstract::Adult T-cell leukemia/lymphoma (ATLL) is a malignancy of mature T cells associated with chronic infection by human T-cell lymphotropic virus type-1 (HTLV-1). ATLL patients with aggressive subtypes have dismal outcomes. We demonstrate that ATLL cells co-opt an early checkpoint within the tumor necrosis factor receptor ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2294-6
更新日期:2020-02-05 00:00:00
abstract::Back pain is a leading cause of global disability and is strongly associated with intervertebral disc (IVD) degeneration (IDD). Hallmarks of IDD include progressive cell loss and matrix degradation. The Akt signaling pathway regulates cellularity and matrix production in IVDs and its inactivation is known to contribut...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1985-3
更新日期:2019-10-03 00:00:00
abstract::Although targeting of the death receptors (DRs) DR4 and DR5 still appears a suitable antitumoral strategy, the limited clinical responses to recombinant soluble TNF-related apoptosis inducing ligand (TRAIL) necessitate novel reagents with improved apoptotic activity/tumor selectivity. Apoptosis induction by a single-c...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2012.29
更新日期:2012-04-12 00:00:00
abstract::Adrenomedullin (ADM) exerts anti-oxidant, anti-inflammatory and anti-apoptotic effects in Leydig cells. However, the role and mechanism of ADM in the pyroptosis of Leydig cells are poorly understood. This study first showed the protective effects of ADM on the pyroptosis and biological functions of Leydig cells expose...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1728-5
更新日期:2019-06-20 00:00:00
abstract::The unfolded protein response (UPR) triggered by endoplasmic reticulum (ER) stress is a feature of many neurodegenerative diseases including Alzheimer's disease, Huntington's disease and Parkinson's disease (PD). Although the vast majority of PD is sporadic, mutations in a number of genes including PARK7 which encodes...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1354-2
更新日期:2019-02-12 00:00:00
abstract::In the healthcare sector, phytocompounds are known to be beneficial by contributing or alleviating a variety of diseases. Studies have demonstrated the progressive effects of phytocompounds on immune-related diseases and to exhibit anticancer effects. Graviola tree is an evergreen tree with its extracts (leafs and see...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0772-x
更新日期:2018-07-09 00:00:00
abstract::Hyperoxia treatment has been known to induce neuronal and glial death in the developing central nervous system. Retinopathy of prematurity (ROP) is a devastating disease in premature infants and a major cause of childhood vision impairment. Studies indicate that, in addition to vascular injury, retinal neurons are als...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.23
更新日期:2014-02-20 00:00:00
abstract::Tumor-associated macrophages (TAMs) are frequently found near pancreatic cancer cells, but it is uncertain whether they are involved in pancreatic cancer progression and the Warburg effect. Here, we show that CCL18 secreted by TAMs facilitates malignant progression and induced a glycolytic phenotype in pancreatic canc...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0486-0
更新日期:2018-05-01 00:00:00
abstract::Ewing sarcoma (ES) is the second most frequent childhood bone cancer driven by the EWS/FLI1 (EF) fusion protein. Genetically defined ES models are needed to understand how EF expression changes bone precursor cell differentiation, how ES arises and through which mechanisms of inhibition it can be targeted. We used mes...
journal_title:Cell death & disease
pub_type: 杂志文章,收录出版
doi:10.1038/cddis.2016.268
更新日期:2016-10-13 00:00:00
abstract::Therapeutic adoptive transfer of natural regulatory T cells (nTreg, CD4+ CD25+ Foxp3+ T cells) or in vivo selective expansion of nTreg cells has been demonstrated to improve the cardiac function in various cardiovascular disease models. The differentiation of nTreg cells is mediated by catecholamines via β1-adrenergic...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-1209-2
更新日期:2019-02-15 00:00:00
abstract::The proapoptotic protein, prostate apoptosis response-4 (Par-4), acts as a tumor suppressor in prostate cancer cells. The serine/threonine kinase casein kinase 2 (CK2) has a well-reported role in prostate cancer resistance to apoptotic agents or anticancer drugs. However, the mechanistic understanding on how CK2 suppo...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.532
更新日期:2014-01-23 00:00:00