Dysregulated Kras/YY1/ZNF322A/Shh transcriptional axis enhances neo-angiogenesis to promote lung cancer progression.

Abstract:

:Angiogenesis enhances cancer metastasis and progression, however, the roles of transcription regulation in angiogenesis are not fully defined. ZNF322A is an oncogenic zinc-finger transcription factor. Here, we demonstrate a new mechanism of Kras mutation-driven ZNF322A transcriptional activation and elucidate the interplay between ZNF322A and its upstream transcriptional regulators and downstream transcriptional targets in promoting neo-angiogenesis. Methods: Luciferase activity, RT-qPCR and ChIP-qPCR assays were used to examine transcription regulation in cell models. In vitro and in vivo angiogenesis assays were conducted. Immunohistochemistry, Kaplan-Meier method and multivariate Cox regression assays were performed to examine the clinical correlation in tumor specimens from lung cancer patients. Results: We validated that Yin Yang 1 (YY1) upregulated ZNF322A expression through targeting its promoter in the context of Kras mutation. Reconstitution experiments by knocking down YY1 under KrasG13V activation decreased KrasG13V-promoted cancer cell migration, proliferation and ZNF322A promoter activity. Knockdown of YY1 or ZNF322A attenuated angiogenesis in vitro and in vivo. Notably, we validated that ZNF322A upregulated the expression of sonic hedgehog (Shh) gene which encodes a secreted factor that activates pro-angiogenic responses in endothelial cells. Clinically, ZNF322A protein expression positively correlated with Shh and CD31, an endothelial cell marker, in 133 lung cancer patient samples determined using immunohistochemistry analysis. Notably, patients with concordantly high expression of ZNF322A, Shh and CD31 correlated with poor prognosis. Conclusions: These findings highlight the mechanism by which dysregulation of Kras/YY1/ZNF322/Shh transcriptional axis enhances neo-angiogenesis and cancer progression in lung cancer. Therapeutic strategies that target Kras/YY1/ZNF322A/Shh signaling axis may provide new insight on targeted therapy for lung cancer patients.

journal_name

Theranostics

journal_title

Theranostics

authors

Lin CC,Kuo IY,Wu LT,Kuan WH,Liao SY,Jen J,Yang YE,Tang CW,Chen YR,Wang YC

doi

10.7150/thno.47491

subject

Has Abstract

pub_date

2020-08-08 00:00:00

pages

10001-10015

issue

22

issn

1838-7640

pii

thnov10p10001

journal_volume

10

pub_type

杂志文章
  • "Navigate-dock-activate" anti-tumor strategy: Tumor micromilieu charge-switchable, hierarchically activated nanoplatform with ultrarapid tumor-tropic accumulation for trackable photothermal/chemotherapy.

    abstract::The delivery of therapeutics into tumors remains a challenge in nanoparticle-mediated drug delivery. However, effective therapies such as photothermal therapy (PTT) are limited by quick systemic clearance and non-specific biodistribution. Anti-tumor strategies tailored to accommodate both tumor accumulation/retention ...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.33280

    authors: Cherukula K,Uthaman S,Park IK

    更新日期:2019-04-13 00:00:00

  • A Comprehensive Study of Vesicular and Non-Vesicular miRNAs from a Volume of Cerebrospinal Fluid Compatible with Clinical Practice.

    abstract::Cerebrospinal fluid (CSF) microRNAs (miRNAs) have emerged as potential biomarkers for minimally invasive diagnosis of central nervous system malignancies. However, despite significant advances in recent years, this field still suffers from poor data reproducibility. This is especially true in cases of infants, conside...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.31502

    authors: Prieto-Fernández E,Aransay AM,Royo F,González E,Lozano JJ,Santos-Zorrozua B,Macias-Camara N,González M,Garay RP,Benito J,Garcia-Orad A,Falcón-Pérez JM

    更新日期:2019-06-19 00:00:00

  • Pancreatic stellate cells activated by mutant KRAS-mediated PAI-1 upregulation foster pancreatic cancer progression via IL-8.

    abstract::Background: The dense fibrotic stroma enveloping pancreatic tumors is a major cause of drug resistance. Pancreatic stellate cells (PSCs) in the stroma can be activated to induce intra-tumor fibrosis and worsen patient survival; however, the molecular basics for the regulation of PSC activation remains unclear. Methods...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.36830

    authors: Wang HC,Lin YL,Hsu CC,Chao YJ,Hou YC,Chiu TJ,Huang PH,Tang MJ,Chen LT,Shan YS

    更新日期:2019-09-23 00:00:00

  • Clinical Applications of NanoVelcro Rare-Cell Assays for Detection and Characterization of Circulating Tumor Cells.

    abstract::Liquid biopsy of tumor through isolation of circulating tumor cells (CTCs) allows non-invasive, repetitive, and systemic sampling of disease. Although detecting and enumerating CTCs is of prognostic significance in metastatic cancer, it is conceivable that performing molecular and functional characterization on CTCs w...

    journal_title:Theranostics

    pub_type: 杂志文章,评审

    doi:10.7150/thno.15359

    authors: Chen JF,Zhu Y,Lu YT,Hodara E,Hou S,Agopian VG,Tomlinson JS,Posadas EM,Tseng HR

    更新日期:2016-06-15 00:00:00

  • Lentivirus-mediated IL-10-expressing Bone Marrow Mesenchymal Stem Cells promote corneal allograft survival via upregulating lncRNA 003946 in a rat model of corneal allograft rejection.

    abstract::Rationale: Corneal transplantation is an effective treatment to corneal blindness. However, the immune rejection imperils corneal allograft survival. An interventional modality is urgently needed to inhibit immune rejection and promote allograft survival. In our previous study, subconjunctival injections of bone marro...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.31711

    authors: Lu X,Ru Y,Chu C,Lv Y,Gao Y,Jia Z,Huang Y,Zhang Y,Zhao S

    更新日期:2020-07-09 00:00:00

  • Recent Progress in Light-Triggered Nanotheranostics for Cancer Treatment.

    abstract::Treatments of high specificity are desirable for cancer therapy. Light-triggered nanotheranostics (LTN) mediated cancer therapy could be one such treatment, as they make it possible to visualize and treat the tumor specifically in a light-controlled manner with a single injection. Because of their great potential in c...

    journal_title:Theranostics

    pub_type: 杂志文章,评审

    doi:10.7150/thno.15217

    authors: Zhang P,Hu C,Ran W,Meng J,Yin Q,Li Y

    更新日期:2016-04-27 00:00:00

  • A Combination of DNA-peptide Probes and Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS): A Quasi-Targeted Proteomics Approach for Multiplexed MicroRNA Quantification.

    abstract::The distorted and unique expression of microRNAs (miRNAs) in cancer makes them an attractive source of biomarker. There is much evidence indicating that a panel of miRNAs, termed "miRNA fingerprints", is more specific and informative than an individual miRNA as biomarker. Thus, multiplex assays for simultaneous quanti...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.19113

    authors: Xu F,Zhou W,Cao J,Xu Q,Jiang D,Chen Y

    更新日期:2017-07-08 00:00:00

  • Size-dependent Effects of Gold Nanoparticles on Osteogenic Differentiation of Human Periodontal Ligament Progenitor Cells.

    abstract::Gold nanoparticles (AuNPs) have been reported to promote osteogenic differentiation of mesenchymal stem cells and osteoblasts, but little is known about their effects on human periodontal ligament progenitor cells (PDLPs). In this study, we evaluated the effects of AuNPs with various diameters (5, 13 and 45 nm) on the...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.17252

    authors: Zhang Y,Kong N,Zhang Y,Yang W,Yan F

    更新日期:2017-03-06 00:00:00

  • Modulation of Respiration and Mitochondrial Dynamics by SMAC-Mimetics for Combination Therapy in Chemoresistant Cancer.

    abstract::Inhibitor of apoptosis proteins (IAP) are cell death regulators that bind caspases and interfere with apoptotic signalling via death receptors or intrinsic cell death pathways. BIRC4/XIAP is the most potent anti-apoptotic IAP-member and it physically interacts with caspases via its BIR2 and its BIR3 domain. These doma...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.33758

    authors: Hagenbuchner J,Oberacher H,Arnhard K,Kiechl-Kohlendorfer U,Ausserlechner MJ

    更新日期:2019-07-09 00:00:00

  • Anti-tumor Efficiency of Lipid-coated Cisplatin Nanoparticles Co-loaded with MicroRNA-375.

    abstract::One of the major challenges in the hepatocellular carcinoma (HCC) treatment is its insensitivity to chemotherapeutic drugs. Here, we report the development of novel lipid-coated cisplatin nanoparticles co-loaded with microRNA-375 (NPC/miR-375) as a potential treatment for chemotherapy insensitive HCC. The NPC/miR-375 ...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.13130

    authors: Yang T,Zhao P,Rong Z,Li B,Xue H,You J,He C,Li W,He X,Lee RJ,Ma X,Xiang G

    更新日期:2016-01-01 00:00:00

  • Gadofullerene nanoparticles for robust treatment of aplastic anemia induced by chemotherapy drugs.

    abstract::Aplastic anemia (AA) is characterized as hypoplasia of bone marrow hematopoietic cells and hematopenia of peripheral blood cells. Though the supplement of exogenous erythropoietin (EPO) has been clinically approved for AA treatment, the side-effects hinder its further application. Here a robust treatment for AA induce...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.46794

    authors: Jia W,Zhen M,Li L,Zhou C,Sun Z,Liu S,Zhao Z,Li J,Wang C,Bai C

    更新日期:2020-05-23 00:00:00

  • Lymphocytic subsets play distinct roles in heart diseases.

    abstract::Heart diseases are one of the leading causes of death for humans in the world. Increasing evidence has shown that myocardial injury induced innate and adaptive immune responses upon early cellular damage but also during chronic phases post-injury. The immune cells can not only aggravate the injury but also play an ess...

    journal_title:Theranostics

    pub_type: 杂志文章,评审

    doi:10.7150/thno.33112

    authors: Wang J,Duan Y,Sluijter JP,Xiao J

    更新日期:2019-05-31 00:00:00

  • Dual-Modality ImmunoPET/Fluorescence Imaging of Prostate Cancer with an Anti-PSCA Cys-Minibody.

    abstract::Inadequate diagnostic methods for prostate cancer lead to over- and undertreatment, and the inability to intraoperatively visualize positive margins may limit the success of surgical resection. Prostate cancer visualization could be improved by combining the complementary modalities of immuno-positron emission tomogra...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.27679

    authors: Tsai WK,Zettlitz KA,Tavaré R,Kobayashi N,Reiter RE,Wu AM

    更新日期:2018-11-12 00:00:00

  • Shape-, size- and structure-controlled synthesis and biocompatibility of iron oxide nanoparticles for magnetic theranostics.

    abstract::In the past decade, iron oxide nanoparticles (IONPs) have attracted more and more attention for their excellent physicochemical properties and promising biomedical applications. In this review, we summarize and highlight recent progress in the design, synthesis, biocompatibility evaluation and magnetic theranostic app...

    journal_title:Theranostics

    pub_type: 杂志文章,评审

    doi:10.7150/thno.25220

    authors: Xie W,Guo Z,Gao F,Gao Q,Wang D,Liaw BS,Cai Q,Sun X,Wang X,Zhao L

    更新日期:2018-05-11 00:00:00

  • All-stage precisional glioma targeted therapy enabled by a well-designed D-peptide.

    abstract::Uncontrollable cell proliferation and irreversible neurological damage make glioma one of the most deadly diseases in clinic. Besides the multiple biological barriers, glioma stem cells (GSCs) that are responsible for the maintenance and recurrence of tumor tissues also hinder the therapeutic efficacy of chemotherapy....

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.41382

    authors: Ran D,Zhou J,Chai Z,Li J,Xie C,Mao J,Lu L,Zhang Y,Wu S,Zhan C,Lu W

    更新日期:2020-03-04 00:00:00

  • VEGFC acts as a double-edged sword in renal cell carcinoma aggressiveness.

    abstract::Hypoxic zones are common features of metastatic tumors. Due to inactivation of the von Hippel-Lindau gene (VHL), renal cell carcinomas (RCC) show constitutive stabilization of the alpha subunit of the hypoxia-inducible factor (HIF). Thus, RCC represents a model of chronic hypoxia. Development of the lymphatic network ...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.27794

    authors: Ndiaye PD,Dufies M,Giuliano S,Douguet L,Grépin R,Durivault J,Lenormand P,Glisse N,Mintcheva J,Vouret-Craviari V,Mograbi B,Wurmser M,Ambrosetti D,Rioux-Leclercq N,Maire P,Pagès G

    更新日期:2019-01-21 00:00:00

  • ROS-Responsive Mitochondria-Targeting Blended Nanoparticles: Chemo- and Photodynamic Synergistic Therapy for Lung Cancer with On-Demand Drug Release upon Irradiation with a Single Light Source.

    abstract::Mitochondria in cancer cells maintain a more negative membrane potential than normal cells. Mitochondria are the primary source of cellular reactive oxygen species (ROS), which are necessary for photodynamic therapy. Thus, the strategy of targeting mitochondria can maximize the photodynamic therapeutic efficiency for ...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.15433

    authors: Yue C,Yang Y,Zhang C,Alfranca G,Cheng S,Ma L,Liu Y,Zhi X,Ni J,Jiang W,Song J,de la Fuente JM,Cui D

    更新日期:2016-10-01 00:00:00

  • Charge and hydrophobicity effects of NIR fluorophores on bone-specific imaging.

    abstract::Recent advances in near-infrared (NIR) fluorescence imaging enabled real-time intraoperative detection of bone metastases, bone growth, and tissue microcalcification. Pamidronate (PAM) has been widely used for this purpose because of its high binding affinity toward bone and remarkable therapeutic effects. Herein we d...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.11222

    authors: Bao K,Nasr KA,Hyun H,Lee JH,Gravier J,Gibbs SL,Choi HS

    更新日期:2015-03-01 00:00:00

  • An Activatable Near-Infrared Chromophore for Multispectral Optoacoustic Imaging of Tumor Hypoxia and for Tumor Inhibition.

    abstract::Hypoxia is a key hallmark of solid tumors and tumor hypoxia usually contributes to cancer progression, therapeutic resistance and poor outcome. Accurately detecting and imaging tumor hypoxia with high spatial resolution would be conducive to formulating optimized treatment plan and thus achieving better patient outcom...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.36755

    authors: Huang J,Wu Y,Zeng F,Wu S

    更新日期:2019-09-25 00:00:00

  • PI3K-AKT-mTOR-signaling and beyond: the complex network in gastroenteropancreatic neuroendocrine neoplasms.

    abstract::Gastroenteropancreatic neuroendocrine neoplasms are heterogeneous in their clinical behavior and require therapies specially tailored according to staging, grading, origin and expression of peptide receptors. Despite extensive scientific efforts, the therapy options are still not satisfactory. The main reasons are due...

    journal_title:Theranostics

    pub_type: 杂志文章,评审

    doi:10.7150/thno.7851

    authors: Briest F,Grabowski P

    更新日期:2014-01-29 00:00:00

  • Discrete functional and mechanistic roles of chromodomain Y-like 2 (CDYL2) transcript variants in breast cancer growth and metastasis.

    abstract::Rationale: Chromodomain Y-like 2 (CDYL2) is a member of the CDY gene family involved in spermatogenesis, but its role in human cancer has not been reported. Analyses of publicly available databases demonstrate that CDYL2 is abundantly expressed in breast tumors. However, whether CDYL2 is involved in breast cancer prog...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.43744

    authors: Yang LF,Yang F,Zhang FL,Xie YF,Hu ZX,Huang SL,Shao ZM,Li DQ

    更新日期:2020-04-06 00:00:00

  • Targeting Epstein-Barr virus oncoprotein LMP1-mediated high oxidative stress suppresses EBV lytic reactivation and sensitizes tumors to radiation therapy.

    abstract::Generating oxidative stress is a critical mechanism by which host cells defend against infection by pathogenic microorganisms. Radiation resistance is a critical problem in radiotherapy against cancer. Epstein-Barr virus (EBV) is a cancer-causing virus and its reactivation plays an important role in the development of...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.46006

    authors: Hu J,Li Y,Li H,Shi F,Xie L,Zhao L,Tang M,Luo X,Jia W,Fan J,Zhou J,Gao Q,Qiu S,Wu W,Zhang X,Liao W,Bode AM,Cao Y

    更新日期:2020-10-25 00:00:00

  • Enhancement of mitochondrial ROS accumulation and radiotherapeutic efficacy using a Gd-doped titania nanosensitizer.

    abstract::Radiotherapy is an extensively used treatment modality in the clinic and can kill malignant cells by generating cytotoxic reactive oxygen species (ROS). Unfortunately, excessive dosages of radiation are typically required because only a small proportion of the radiative energy is adsorbed by the soft tissues of a tumo...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.28033

    authors: Chen Y,Li N,Wang J,Zhang X,Pan W,Yu L,Tang B

    更新日期:2019-01-01 00:00:00

  • Real time dynamic imaging and current targeted therapies in the war on cancer: a new paradigm.

    abstract::In biology, as every science student is made to learn, ontology recapitulates phylogeny. In medicine, however, oncology recapitulates polemology, the science of warfare: The medical establishment is transitioning from highly toxic poisons that kill rapidly dividing normal and malignant cells with little specificity to...

    journal_title:Theranostics

    pub_type: 杂志文章,评审

    doi:10.7150/thno.5658

    authors: Paulmurugan R,Oronsky B,Brouse CF,Reid T,Knox S,Scicinski J

    更新日期:2013-05-25 00:00:00

  • Tumour Vascular Shutdown and Cell Death Following Ultrasound-Microbubble Enhanced Radiation Therapy.

    abstract::High-dose radiotherapy effects are regulated by acute tumour endothelial cell death followed by rapid tumour cell death instead of canonical DNA break damage. Pre-treatment with ultrasound-stimulated microbubbles (USMB) has enabled higher-dose radiation effects with conventional radiation doses. This study aimed to co...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.19010

    authors: El Kaffas A,Gangeh MJ,Farhat G,Tran WT,Hashim A,Giles A,Czarnota GJ

    更新日期:2018-01-01 00:00:00

  • Adaptive changes induced by noble-metal nanostructures in vitro and in vivo.

    abstract::The unique features of noble-metal nanostructures (NMNs) are leading to unprecedented expansion of research and exploration of their application in therapeutics, diagnostics and bioimaging fields. With the ever-growing applications of NMNs, both therapeutic and environmental NMNs are likely to be exposed to tissues an...

    journal_title:Theranostics

    pub_type: 杂志文章,评审

    doi:10.7150/thno.42569

    authors: Huang Q,Zhang J,Zhang Y,Timashev P,Ma X,Liang XJ

    更新日期:2020-04-27 00:00:00

  • PLAGL2 promotes the proliferation and migration of gastric cancer cells via USP37-mediated deubiquitination of Snail1.

    abstract::Rationale: PLAGL2 (pleomorphic adenoma gene like-2), a zinc finger PLAG transcription factor, is aberrantly expressed in several malignant tumors. However, the biological roles of PLAGL2 and its underlying mechanism in gastric cancer (GC) remain unclear. Methods: A series of experiments in vitro and in vivo were condu...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.47800

    authors: Wu L,Zhao N,Zhou Z,Chen J,Han S,Zhang X,Bao H,Yuan W,Shu X

    更新日期:2021-01-01 00:00:00

  • YTHDF1-enhanced iron metabolism depends on TFRC m6A methylation.

    abstract::Background: Among head and neck squamous cell carcinomas (HNSCCs), hypopharyngeal squamous cell carcinoma (HPSCC) has the worst prognosis. Iron metabolism, which plays a crucial role in tumor progression, is mainly regulated by alterations to genes and post-transcriptional processes. The recent discovery of the N6-met...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.51231

    authors: Ye J,Wang Z,Chen X,Jiang X,Dong Z,Hu S,Li W,Liu Y,Liao B,Han W,Shen J,Xiao M

    更新日期:2020-10-26 00:00:00

  • The cytotoxic effects of dimethyl sulfoxide in mouse preimplantation embryos: a mechanistic study.

    abstract::Rationale: Dimethyl sulfoxide (DMSO) is commonly used as a solvent for water-insoluble substances, a vehicle for drug therapy, and a cryoprotectant for cultured cells. DMSO induced embryonic defects and its mechanism of action remains unclear. The rationale is based on the assumption that DMSO supplementation should i...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.21662

    authors: Kang MH,Das J,Gurunathan S,Park HW,Song H,Park C,Kim JH

    更新日期:2017-10-17 00:00:00

  • A paclitaxel prodrug with bifunctional folate and albumin binding moieties for both passive and active targeted cancer therapy.

    abstract::Folate receptor (FR) has proven to be a valuable target for chemotherapy using folic acid (FA) conjugates. However, FA-conjugated chemotherapeutics still have low therapeutic efficacy accompanied with side effects, resulting from complications such as short circulation half-life, limited tumor delivery, as well as hig...

    journal_title:Theranostics

    pub_type: 杂志文章

    doi:10.7150/thno.24382

    authors: Shan L,Zhuo X,Zhang F,Dai Y,Zhu G,Yung BC,Fan W,Zhai K,Jacobson O,Kiesewetter DO,Ma Y,Gao G,Chen X

    更新日期:2018-02-16 00:00:00