LncRNA TTN-AS1 promotes migration, invasion, and epithelial mesenchymal transition of lung adenocarcinoma via sponging miR-142-5p to regulate CDK5.

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 adenocarcinoma (LUAD) remain unclear. In the present study, we revealed that the expression of TTN-AS1 was upregulated in LUAD tissues and cell lines. High TTN-AS1 expression was associated with TNM stage and lymph node metastasis of LUAD patients. In addition, high expression of TTN-AS1 was correlated with poor postoperative prognosis of LUAD patients. Knockdown of TTN-AS1 significantly inhibited the growth, proliferation, migration, and invasion ability of LUAD cells in vitro. Then, by using bioinformation analysis and luciferase reporter experiment, we identified that TTN-AS1 could function as a competing endogenous RNA (ceRNA) by sponging miR-142-5p to regulate the expression of cyclin-dependent kinase 5 (CDK5) in LUAD. Since CDK5 is a key regulator in the process of epithelial mesenchymal transition (EMT), we detected the expression of EMT-related proteins, consequently, EMT was suppressed by knockdown of TTN-AS1 while this phenomenon was rescued by miR-142-5p inhibitor. Taken above, our study revealed that TTN-AS1 played an important role in LUAD progression. TTN-AS1/miR-142-5p/CDK5 regulatory axis may serve as a novel therapeutic target in the treatment of LUAD.

journal_name

Cell Death Dis

journal_title

Cell death & disease

authors

Jia Y,Duan Y,Liu T,Wang X,Lv W,Wang M,Wang J,Liu L

doi

10.1038/s41419-019-1811-y

subject

Has Abstract

pub_date

2019-07-30 00:00:00

pages

573

issue

8

issn

2041-4889

pii

10.1038/s41419-019-1811-y

journal_volume

10

pub_type

杂志文章
  • MDM2 prevents spontaneous tubular epithelial cell death and acute kidney injury.

    abstract::Murine double minute-2 (MDM2) is an E3-ubiquitin ligase and the main negative regulator of tumor suppressor gene p53. MDM2 has also a non-redundant function as a modulator of NF-kB signaling. As such it promotes proliferation and inflammation. MDM2 is highly expressed in the unchallenged tubular epithelial cells and w...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2016.390

    authors: Thomasova D,Ebrahim M,Fleckinger K,Li M,Molnar J,Popper B,Liapis H,Kotb AM,Siegerist F,Endlich N,Anders HJ

    更新日期:2016-11-24 00:00:00

  • Melatonin inhibits apoptotic cell death induced by Vibrio vulnificus VvhA via melatonin receptor 2 coupling with NCF-1.

    abstract::Melatonin, an endogenous hormone molecule, has a variety of biological functions, but a functional role of melatonin in the infection of Gram-negative bacterium Vibrio vulnificus has yet to be described. In this study, we investigated the molecular mechanism of melatonin in the apoptosis of human intestinal epithelial...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-017-0083-7

    authors: Lee SJ,Lee HJ,Jung YH,Kim JS,Choi SH,Han HJ

    更新日期:2018-01-19 00:00:00

  • Insulin-like growth factor binding proteins 4 and 7 released by senescent cells promote premature senescence in mesenchymal stem cells.

    abstract::Cellular senescence is the permanent arrest of cell cycle, physiologically related to aging and aging-associated diseases. Senescence is also recognized as a mechanism for limiting the regenerative potential of stem cells and to protect cells from cancer development. The senescence program is realized through autocrin...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2013.445

    authors: Severino V,Alessio N,Farina A,Sandomenico A,Cipollaro M,Peluso G,Galderisi U,Chambery A

    更新日期:2013-11-07 00:00:00

  • Chronic restraint stress decreases the repair potential from mesenchymal stem cells on liver injury by inhibiting TGF-β1 generation.

    abstract::Chronic psychological stress has been demonstrated to play an important role in several severe diseases, but whether it affects disease therapy or not remains unclear. Mesenchymal stem cells (MSCs) have been demonstrated to have therapeutic potentials in treating tissue injury based on their multidifferentiation poten...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2014.257

    authors: Yang X,Han ZP,Zhang SS,Zhu PX,Hao C,Fan TT,Yang Y,Li L,Shi YF,Wei LX

    更新日期:2014-06-26 00:00:00

  • SOX4 contributes to the progression of cervical cancer and the resistance to the chemotherapeutic drug through ABCG2.

    abstract::SOX4, a member of the SOX (sex-determining region Y-related HMG box) transcription factor family, has been reported to be abnormally expressed in a wide variety of cancers, and to exert a pleiotropic function. However, its function in progression of cervical cancer (CC) remains unknown. In this study, we found that SO...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2015.290

    authors: Sun R,Jiang B,Qi H,Zhang X,Yang J,Duan J,Li Y,Li G

    更新日期:2015-11-19 00:00:00

  • PPARγ population shift produces disease-related changes in molecular networks associated with metabolic syndrome.

    abstract::Peroxisome proliferator-activated receptor gamma (PPARγ) is a key regulator of adipocyte differentiation and has an important role in metabolic syndrome. Phosphorylation of the receptor's ligand-binding domain at serine 273 has been shown to change the expression of a large number of genes implicated in obesity. The d...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2011.74

    authors: Jurkowski W,Roomp K,Crespo I,Schneider JG,Del Sol A

    更新日期:2011-08-11 00:00:00

  • TCF3, a novel positive regulator of osteogenesis, plays a crucial role in miR-17 modulating the diverse effect of canonical Wnt signaling in different microenvironments.

    abstract::Wnt signaling pathways are a highly conserved pathway, which plays an important role from the embryonic development to bone formation. The effect of Wnt pathway on osteogenesis relies on their cellular environment and the expression of target genes. However, the molecular mechanism of that remains unclear. On the basi...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2013.65

    authors: Liu W,Liu Y,Guo T,Hu C,Luo H,Zhang L,Shi S,Cai T,Ding Y,Jin Y

    更新日期:2013-03-14 00:00:00

  • Increase in HDAC9 suppresses myoblast differentiation via epigenetic regulation of autophagy in hypoxia.

    abstract::Extremely reduced oxygen (O2) levels are detrimental to myogenic differentiation and multinucleated myotube formation, and chronic exposure to high-altitude hypoxia has been reported to be an important factor in skeletal muscle atrophy. However, how chronic hypoxia causes muscle dysfunction remains unknown. In the pre...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1763-2

    authors: Zhang Z,Zhang L,Zhou Y,Li L,Zhao J,Qin W,Jin Z,Liu W

    更新日期:2019-07-18 00:00:00

  • Human mesenchymal stem cell-replicative senescence and oxidative stress are closely linked to aneuploidy.

    abstract::In most clinical trials, human mesenchymal stem cells (hMSCs) are expanded in vitro before implantation. The genetic stability of human stem cells is critical for their clinical use. However, the relationship between stem-cell expansion and genetic stability is poorly understood. Here, we demonstrate that within the n...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2013.211

    authors: Estrada JC,Torres Y,Benguría A,Dopazo A,Roche E,Carrera-Quintanar L,Pérez RA,Enríquez JA,Torres R,Ramírez JC,Samper E,Bernad A

    更新日期:2013-06-27 00:00:00

  • HCC-derived exosomes elicit HCC progression and recurrence by epithelial-mesenchymal transition through MAPK/ERK signalling pathway.

    abstract::Liver cancer is the second most common cause of cancer-related death worldwide. Approximately 70-90% of primary liver cancers are hepatocellular carcinoma (HCC). Currently, HCC patient prognosis is unsatisfactory due to high metastasis and/or post-surgical recurrence rates. Therefore, new therapeutic methods for inhib...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-0534-9

    authors: Chen L,Guo P,He Y,Chen Z,Chen L,Luo Y,Qi L,Liu Y,Wu Q,Cui Y,Fang F,Zhang X,Song T,Guo H

    更新日期:2018-05-01 00:00:00

  • Inhibition of the MAP3 kinase Tpl2 protects rodent and human β-cells from apoptosis and dysfunction induced by cytokines and enhances anti-inflammatory actions of exendin-4.

    abstract::Proinflammatory cytokines exert cytotoxic effects on β-cells, and are involved in the pathogenesis of type I and type II diabetes and in the drastic loss of β-cells following islet transplantation. Cytokines induce apoptosis and alter the function of differentiated β-cells. Although the MAP3 kinase tumor progression l...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2015.399

    authors: Varin EM,Wojtusciszyn A,Broca C,Muller D,Ravier MA,Ceppo F,Renard E,Tanti JF,Dalle S

    更新日期:2016-01-21 00:00:00

  • The JAK2/STAT3 and mitochondrial pathways are essential for quercetin nanoliposome-induced C6 glioma cell death.

    abstract::The formulation of quercetin nanoliposomes (QUE-NLs) has been shown to enhance QUE antitumor activity in C6 glioma cells. At high concentrations, QUE-NLs induce necrotic cell death. In this study, we probed the molecular mechanisms of QUE-NL-induced C6 glioma cell death and examined whether QUE-NL-induced programmed c...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2013.242

    authors: Wang G,Wang JJ,Chen XL,Du SM,Li DS,Pei ZJ,Lan H,Wu LB

    更新日期:2013-08-01 00:00:00

  • FTSJ1 regulates tRNA 2'-O-methyladenosine modification and suppresses the malignancy of NSCLC via inhibiting DRAM1 expression.

    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 obsc...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-2525-x

    authors: 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 R

    更新日期:2020-05-11 00:00:00

  • Serpina3n attenuates granzyme B-mediated decorin cleavage and rupture in a murine model of aortic aneurysm.

    abstract::Granzyme B (GZMB) is a proapoptotic serine protease that is released by cytotoxic lymphocytes. However, GZMB can also be produced by other cell types and is capable of cleaving extracellular matrix (ECM) proteins. GZMB contributes to abdominal aortic aneurysm (AAA) through an extracellular, perforin-independent mechan...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2011.88

    authors: Ang LS,Boivin WA,Williams SJ,Zhao H,Abraham T,Carmine-Simmen K,McManus BM,Bleackley RC,Granville DJ

    更新日期:2011-09-08 00:00:00

  • KLF17 empowers TGF-β/Smad signaling by targeting Smad3-dependent pathway to suppress tumor growth and metastasis during cancer progression.

    abstract::Inhibition of tumor suppressive signaling is linked to cancer progression, metastasis and epithelial-mesenchymal transition (EMT). Transforming growth factor-β1 (TGF-β)/Smad signaling plays an important role in tumor suppression. Kruppel-like-factor 17 (KLF17) is a negative regulator of metastasis and EMT. However, un...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2015.48

    authors: Ali A,Zhang P,Liangfang Y,Wenshe S,Wang H,Lin X,Dai Y,Feng XH,Moses R,Wang D,Li X,Xiao J

    更新日期:2015-03-12 00:00:00

  • Longikaurin A, a natural ent-kaurane, induces G2/M phase arrest via downregulation of Skp2 and apoptosis induction through ROS/JNK/c-Jun pathway in hepatocellular carcinoma cells.

    abstract::Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer, and is also highly resistant to conventional chemotherapy treatments. In this study, we report that Longikaurin A (LK-A), an ent-kaurane diterpenoid isolated from the plant Isodon ternifolius, induced cell cycle arrest and apoptosis in hum...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2014.66

    authors: Liao YJ,Bai HY,Li ZH,Zou J,Chen JW,Zheng F,Zhang JX,Mai SJ,Zeng MS,Sun HD,Pu JX,Xie D

    更新日期:2014-03-20 00:00:00

  • Modeling radiation injury-induced cell death and countermeasure drug responses in a human Gut-on-a-Chip.

    abstract::Studies on human intestinal injury induced by acute exposure to γ-radiation commonly rely on use of animal models because culture systems do not faithfully mimic human intestinal physiology. Here we used a human Gut-on-a-Chip (Gut Chip) microfluidic device lined by human intestinal epithelial cells and vascular endoth...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-0304-8

    authors: Jalili-Firoozinezhad S,Prantil-Baun R,Jiang A,Potla R,Mammoto T,Weaver JC,Ferrante TC,Kim HJ,Cabral JMS,Levy O,Ingber DE

    更新日期:2018-02-14 00:00:00

  • GSK-3β-induced Tau pathology drives hippocampal neuronal cell death in Huntington's disease: involvement of astrocyte-neuron interactions.

    abstract::Glycogen synthase kinase-3β (GSK-3β) has emerged as a critical factor in several pathways involved in hippocampal neuronal maintenance and function. In Huntington's disease (HD), there are early hippocampal deficits both in patients and transgenic mouse models, which prompted us to investigate whether disease-specific...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2016.104

    authors: L'Episcopo F,Drouin-Ouellet J,Tirolo C,Pulvirenti A,Giugno R,Testa N,Caniglia S,Serapide MF,Cisbani G,Barker RA,Cicchetti F,Marchetti B

    更新日期:2016-04-28 00:00:00

  • Marchantin M: a novel inhibitor of proteasome induces autophagic cell death in prostate cancer cells.

    abstract::We previously reported that marchantin M (Mar) is an active agent to induce apoptosis in human prostate cancer (PCa), but the molecular mechanisms of action remain largely unknown. Here, we demonstrate that Mar potently inhibited chymotrypsin-like and peptidyl-glutamyl peptide-hydrolyzing activities of 20S proteasome ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2013.285

    authors: Jiang H,Sun J,Xu Q,Liu Y,Wei J,Young CY,Yuan H,Lou H

    更新日期:2013-08-08 00:00:00

  • Costello syndrome model mice with a HrasG12S/+ mutation are susceptible to develop house dust mite-induced atopic dermatitis.

    abstract::Costello syndrome is an autosomal dominant disorder that is caused by germline HRAS mutations. Patients with Costello syndrome present craniofacial abnormalities, cardiac defects, and cancer predisposition, as well as skin abnormalities, including papillomas, keratosis pilaris, and eczematous dermatitis. However, the ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-02845-8

    authors: Katata Y,Inoue SI,Asao A,Kobayashi S,Terui H,Inoue-Shibui A,Abe T,Niihori T,Aiba S,Ishii N,Kure S,Aoki Y

    更新日期:2020-08-13 00:00:00

  • The integrity of cochlear hair cells is established and maintained through the localization of Dia1 at apical junctional complexes and stereocilia.

    abstract::Dia1, which belongs to the diaphanous-related formin family, influences a variety of cellular processes through straight actin elongation activity. Recently, novel DIA1 mutants such as p.R1213X (p.R1204X) and p.A265S, have been reported to cause an autosomal dominant sensorineural hearing loss (DFNA1). Additionally, a...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-02743-z

    authors: Ninoyu Y,Sakaguchi H,Lin C,Suzuki T,Hirano S,Hisa Y,Saito N,Ueyama T

    更新日期:2020-07-16 00:00:00

  • The NF-κB1 is a key regulator of acute but not chronic renal injury.

    abstract::The NF-κB family of transcription factors is important for many cellular functions, in particular initiation and propagation of inflammatory and immune responses. However, recent data has suggested that different subunits of the NF-κB family can suppress the inflammatory response. NF-κB1, from the locus nfκb1, can inh...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2017.233

    authors: Fearn A,Situmorang GR,Fox C,Oakley F,Howarth R,Wilson CL,Kiosia A,Robson MG,Mann DA,Moles A,Sheerin NS

    更新日期:2017-06-15 00:00:00

  • Tumorigenic potential is restored during differentiation in fusion-reprogrammed cancer cells.

    abstract::Detailed understanding of the mechanistic steps underlying tumor initiation and malignant progression is critical for insights of potentially novel therapeutic modalities. Cellular reprogramming is an approach of particular interest because it can provide a means to reset the differentiation state of the cancer cells ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2016.189

    authors: Yao J,Zhang L,Hu L,Guo B,Hu X,Borjigin U,Wei Z,Chen Y,Lv M,Lau JT,Wang X,Li G,Hu YP

    更新日期:2016-07-28 00:00:00

  • Cancer-associated fibroblasts enact field cancerization by promoting extratumoral oxidative stress.

    abstract::Histological inspection of visually normal tissue adjacent to neoplastic lesions often reveals multiple foci of cellular abnormalities. This suggests the presence of a regional carcinogenic signal that spreads oncogenic transformation and field cancerization. We observed an abundance of mutagenic reactive oxygen speci...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2016.492

    authors: Chan JS,Tan MJ,Sng MK,Teo Z,Phua T,Choo CC,Li L,Zhu P,Tan NS

    更新日期:2017-01-19 00:00:00

  • Interplay between Caspase 9 and X-linked Inhibitor of Apoptosis Protein (XIAP) in the oocyte elimination during fetal mouse development.

    abstract::Mammalian female fertility is limited by the number and quality of oocytes in the ovarian reserve. The number of oocytes is finite since all germ cells cease proliferation to become oocytes in fetal life. Moreover, 70-80% of the initial oocyte population is eliminated during fetal and neonatal development, restricting...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-2019-x

    authors: Liu X,Castle V,Taketo T

    更新日期:2019-10-17 00:00:00

  • E3 ubiquitin ligase-mediated regulation of bone formation and tumorigenesis.

    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

    doi:10.1038/cddis.2012.217

    authors: Sévère N,Dieudonné FX,Marie PJ

    更新日期:2013-01-17 00:00:00

  • A role for intracellular zinc in glioma alteration of neuronal chloride equilibrium.

    abstract::Glioma patients commonly suffer from epileptic seizures. However, the mechanisms of glioma-associated epilepsy are far to be completely understood. Using glioma-neurons co-cultures, we found that tumor cells are able to deeply influence neuronal chloride homeostasis, by depolarizing the reversal potential of γ-aminobu...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2014.437

    authors: Di Angelantonio S,Murana E,Cocco S,Scala F,Bertollini C,Molinari MG,Lauro C,Bregestovski P,Limatola C,Ragozzino D

    更新日期:2014-10-30 00:00:00

  • ELABELA attenuates deoxycorticosterone acetate/salt-induced hypertension and renal injury by inhibition of NADPH oxidase/ROS/NLRP3 inflammasome pathway.

    abstract::ELABELA (ELA), a 32-residue hormone peptide abundantly expressed in adult kidneys, has been identified as a novel endogenous ligand for APJ/Apelin receptor. The aim of this study was to investigate the role of ELA in deoxycorticosterone acetate (DOCA)/salt-induced hypertension and further explore the underlying mechan...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-02912-0

    authors: Chen Z,Wu C,Liu Y,Li H,Zhu Y,Huang C,Lin H,Qiao Q,Huang M,Zhu Q,Wang L

    更新日期:2020-08-22 00:00:00

  • Phosphorylation of cyclophilin D at serine 191 regulates mitochondrial permeability transition pore opening and cell death after ischemia-reperfusion.

    abstract::The mitochondrial permeability transition pore (mPTP) plays a critical role in the pathogenesis of cardiovascular diseases, including ischemia/reperfusion injury. Although the pore structure is still unresolved, the mechanism through which cyclophilin D (CypD) regulates mPTP opening is the subject of intensive studies...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-02864-5

    authors: Hurst S,Gonnot F,Dia M,Crola Da Silva C,Gomez L,Sheu SS

    更新日期:2020-08-19 00:00:00

  • TBL1 is required for the mesenchymal phenotype of transformed breast cancer cells.

    abstract::The epithelial-to-mesenchymal transition (EMT) and its reversion (MET) are related to tumor cell dissemination and migration, tumor circulating cell generation, cancer stem cells, chemoresistance, and metastasis formation. To identify chromatin and epigenetic factors possibly involved in the process of EMT, we compare...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1310-1

    authors: Rivero S,Gómez-Marín E,Guerrero-Martínez JA,García-Martínez J,Reyes JC

    更新日期:2019-01-31 00:00:00