Antitumor effects of circ-EPHB4 in hepatocellular carcinoma via inhibition of HIF-1α.

Abstract:

:The protein EPHB4 plays a vital role in various tumor types. However, few studies into the function of circ-EPHB4 (hsa_circ_0001730) in tumors have been conducted. This study aimed to investigate the functions of circ-EPHB4 and the underlying mechanism of circ-EPHB4 in regulating hepatocellular carcinoma (HCC). The expression of circ-EPHB4 was found to be downregulated in HCC tumor tissues, whereas circ-EPHB4 overexpression suppressed cell viability, induced apoptosis, and inhibited cell migration and invasion in Huh7 and HepG2 cells. circ-EPHB4 levels were negatively correlated with tumor weight, size, and metastasis foci in nude mouse models, suggesting circ-EPHB4 inhibits tumorigenesis, tumor development, and metastasis. In addition, HIF-1α and PI3K-AKT pathways were markedly affected by circ-EPHB4 overexpression. HIF-1α could potentially be the target of circ-EPHB4. By overexpressing both HIF-1α and circ-EPHB4, the antitumor effect of circ-EPHB4 should be most probably correlated with HIF-1α. In conclusion, circ-EPHB4 is a tumor inhibitor in HCC and functions by inhibiting HIF-1α expression.

journal_name

Mol Carcinog

journal_title

Molecular carcinogenesis

authors

Tan Y,Du B,Zhan Y,Wang K,Wang X,Chen B,Wei X,Xiao J

doi

10.1002/mc.22976

subject

Has Abstract

pub_date

2019-06-01 00:00:00

pages

875-886

issue

6

eissn

0899-1987

issn

1098-2744

journal_volume

58

pub_type

杂志文章
  • A comparative analysis of allelic imbalance events in chemically induced rat mammary, colon, and bladder tumors.

    abstract::In this paper, patterns of allelic imbalances (Als) in chemically induced rat mammary, colon, and bladder tumors from (Wistar Furth x Fischer 344)F1 rats are described and compared. Male F1 rats were administered azoxymethane (AOM), and colon tumors were collected at 58 wk after treatment. Female F1 rats were given ei...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/(sici)1098-2744(199901)24:1<47::aid-mc7>3.

    authors: Haag JD,Brasic GM,Shepel LA,Newton MA,Grubbs CJ,Lubet RA,Kelloff GJ,Gould MN

    更新日期:1999-01-01 00:00:00

  • Plasma lipoxin A4 and resolvin D1 are not associated with reduced adenoma risk in a randomized trial of aspirin to prevent colon adenomas.

    abstract::Inflammation plays a major role in colon carcinogenesis. Endogenously produced specialized proresolving lipid mediators (SPMs) play a central role in inflammation and tissue homeostasis, and have been implicated in carcinogenesis. We studied the associations of plasma levels of two SPMs [lipoxin A4 (LXA4 ) and resolvi...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章,随机对照试验

    doi:10.1002/mc.22629

    authors: Fedirko V,McKeown-Eyssen G,Serhan CN,Barry EL,Sandler RS,Figueiredo JC,Ahnen DJ,Bresalier RS,Robertson DJ,Anderson CW,Baron JA

    更新日期:2017-08-01 00:00:00

  • Centchroman altered the expressions of tumor-related genes through active chromatin modifications in mammary cancer.

    abstract::Centchroman (CC), a female oral contraceptive, has been shown to possess breast anti-cancer activities. Recently, we have shown CC-mediated antimetastatic effect through reversal of epithelial-to-mesenchymal transition (EMT) in breast cancer. The loss of tumor suppressor genes (TSGs) has been shown to promote EMT in b...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22424

    authors: Khan S,Shukla S,Sinha S,Meeran SM

    更新日期:2016-11-01 00:00:00

  • RNA-seq reveals novel cancer-selective and disease subtype-independent mechanistic targets of withaferin A in human breast cancer cells.

    abstract::Withaferin A (WA) exhibits cancer chemopreventive efficacy in preclinical models representative of two different subtypes of breast cancer. However, the mechanism(s) underlying breast cancer chemoprevention by WA is not fully elucidated. We performed RNA-seq analyses using a non-tumorigenic mammary epithelial cell lin...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.23266

    authors: Hahm ER,Kim SH,Singh KB,Singh SV

    更新日期:2021-01-01 00:00:00

  • Inactivation of SNF5 cooperates with p53 loss to accelerate tumor formation in Snf5(+/-);p53(+/-) mice.

    abstract::Malignant rhabdoid tumors (MRTs) are poorly differentiated pediatric cancers that arise in various anatomical locations and have a very poor outcome. The large majority of these malignancies are caused by loss of function of the SNF5/INI1 component of the SWI/SNF chromatin remodeling complex. However, the mechanism of...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20568

    authors: DelBove J,Kuwahara Y,Mora-Blanco EL,Godfrey V,Funkhouser WK,Fletcher CD,Van Dyke T,Roberts CW,Weissman BE

    更新日期:2009-12-01 00:00:00

  • Molecular and immune targets for Merkel cell carcinoma therapy and prevention.

    abstract::Merkel cell carcinoma (MCC) is a rare neuroendocrine carcinoma of the skin, for which the exact mechanisms of carcinogenesis remain unknown. Therapeutic options for this highly aggressive malignancy have historically been limited in both their initial response and response durability. Recent improvements in our unders...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章,评审

    doi:10.1002/mc.23042

    authors: Cohen L,Tsai KY

    更新日期:2019-09-01 00:00:00

  • Persistent infection of hepatitis B virus is involved in high rate of p16 methylation in hepatocellular carcinoma.

    abstract::High rate of chronic hepatitis B virus (HBV) infection and p16 promoter methylation were found in the majority of hepatocellular carcinoma (HCC). To investigate the potential linkage between high rate of p16 methylation and HBV infection, p16 methylation was detected with methylation-specific polymerase chain reaction...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20188

    authors: Jicai Z,Zongtao Y,Jun L,Haiping L,Jianmin W,Lihua H

    更新日期:2006-07-01 00:00:00

  • LW-213 induces G2/M cell cycle arrest through AKT/GSK3β/β-catenin signaling pathway in human breast cancer cells.

    abstract::LW-213 is a derivative of Wogonin and the anticancer activities of Wogonin have been reported. To study whether LW-213 inhibits cancer cells and explore a possible mechanism, we investigate the compound in several cancer cell lines. We found LW-213 arrests G2/M cycle in breast cancer cells by suppression of Akt/Gsk3β/...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22321

    authors: Zhao L,Miao HC,Li WJ,Sun Y,Huang SL,Li ZY,Guo QL

    更新日期:2016-05-01 00:00:00

  • Models for chromosomal replication-independent non-B DNA structure-induced genetic instability.

    abstract::Regions of genomic DNA containing repetitive nucleotide sequences can adopt a number of different structures in addition to the canonical B-DNA form: many of these non-B DNA structures are causative factors in genetic instability and human disease. Although chromosomal DNA replication through such repetitive sequences...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章,评审

    doi:10.1002/mc.20508

    authors: Wang G,Vasquez KM

    更新日期:2009-04-01 00:00:00

  • Modification of p27 with O-linked N-acetylglucosamine regulates cell proliferation in hepatocellular carcinoma.

    abstract::The tumor suppressor p27, which is a member of the Cip/Kip family of Cyclin-dependent kinase inhibitory proteins (CKIs), controls anti-proliferative events. The post-translational addition of O-GlcNAc to p27 occurs in HEK293T and HCC (hepatocellular carcinoma) cell lines, and we identified Ser2, Ser106, Ser110, Thr157...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22490

    authors: Qiu H,Liu F,Tao T,Zhang D,Liu X,Zhu G,Xu Z,Ni R,Shen A

    更新日期:2017-01-01 00:00:00

  • An in vitro system to characterize prostate cancer progression identified signaling required for self-renewal.

    abstract::Mutations in RB and PTEN are linked to castration resistance and poor prognosis in prostate cancer. Identification of genes that are regulated by these tumor suppressors in a context that recapitulates cancer progression may be beneficial for discovering novel therapeutic targets. Although various genetically engineer...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22444

    authors: Salah M,Nishimoto Y,Kohno S,Kondoh A,Kitajima S,Muranaka H,Nishiuchi T,Ibrahim A,Yoshida A,Takahashi C

    更新日期:2016-12-01 00:00:00

  • Dual use of hematopoietic and mesenchymal stem cells enhances engraftment and immune cell trafficking in an allogeneic humanized mouse model of head and neck cancer.

    abstract::In this report, we describe in detail the evolving procedures to optimize humanized mouse cohort generation, including optimal conditioning, choice of lineage for engraftment, threshold for successful engraftment, HNSCC tumor implantation, and immune and stroma cell analyses. We developed a dual infusion protocol of h...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22887

    authors: Morton JJ,Keysar SB,Perrenoud L,Chimed TS,Reisinger J,Jackson B,Le PN,Nieto C,Gomez K,Miller B,Gao D,Somerset H,Wang XJ,Jimeno A

    更新日期:2018-11-01 00:00:00

  • Association of tumorigenic and nontumorigenic (immunogenic) variants in a mouse T-cell lymphoma with two distinct p53 mutations.

    abstract::An in vitro model system for xenogenization has been developed in which an immunogenic, nonmalignant phenotype was selected from a highly malignant T-cell line (S49). We showed by single-strand conformation polymorphism and DNA sequence analysis that specific point mutations in the p53 tumor suppressor gene correlated...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.2940080404

    authors: Bergel M,Bhatia K,Siwarski D,Gutierrez M,Hochman J,Huppi K

    更新日期:1993-01-01 00:00:00

  • LncAPC drives Wnt/β-catenin activation and liver TIC self-renewal through EZH2 mediated APC transcriptional inhibition.

    abstract::Liver tumor initiating cells (TICs), a small subset cells in tumor bulk, are responsible for liver tumor initiation, metastasis, and relapse. However, the regulatory mechanism of liver TICs remains largely unknown. Here we found a long noncoding RNA lncAPC, locating near from APC locus, was highly expressed in liver c...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22764

    authors: Fu X,Lin J,Qin F,Yang Z,Ding Y,Zhang Y,Han L,Zhu X,Zhang Q

    更新日期:2018-03-01 00:00:00

  • LncRNA DANCR promotes tumor growth and angiogenesis in ovarian cancer through direct targeting of miR-145.

    abstract::Differentiation antagonizing non-protein coding RNA (DANCR) is a newly identified oncogenic long noncoding RNA found in various cancers. However, the functional role of DANCR in tumor angiogenesis and the underlying mechanisms are still unclear. The expression of DANCR was determined in ovarian malignant tissues and c...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.23117

    authors: Lin X,Yang F,Qi X,Li Q,Wang D,Yi T,Yin R,Zhao X,Zhong X,Bian C

    更新日期:2019-12-01 00:00:00

  • Induction of glutathione s-transferase-pi in Barrett's metaplasia and Barrett's adenocarcinoma cell lines.

    abstract::Barrett's metaplasia consists of columnar epithelium that replaces the normal esophageal mucosa in patients with chronic gastroesophageal reflux. Because intestinal-type Barrett's metaplasia is the major risk factor for adenocarcinoma development, understanding the mechanisms that predispose the esophageal mucosa to m...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/(sici)1098-2744(199902)24:2<128::aid-mc7>3

    authors: Compton KR,Orringer MB,Beer DG

    更新日期:1999-02-01 00:00:00

  • Genetic variant rs16430 6bp > 0bp at the microRNA-binding site in TYMS and risk of sporadic breast cancer risk in non-Hispanic white women aged ≤ 55 years.

    abstract::Thymidylate synthase (TYMS) is involved in the folate metabolism and provision of nucleotides needed for DNA synthesis and repair. Thus, functional genetic variants in TYMS may alter cancer risk. In the study, we evaluated associations of three germline variants (rs2790 A > G, rs16430 6 bp > 0 bp, and rs1059394 C > T)...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22097

    authors: Guan X,Liu H,Ju J,Li Y,Li P,Wang LE,Brewster AM,Buchholz TA,Arun BK,Wei Q,Liu Z

    更新日期:2015-04-01 00:00:00

  • Phenylbutyl isoselenocyanate induces reactive oxygen species to inhibit androgen receptor and to initiate p53-mediated apoptosis in LNCaP prostate cancer cells.

    abstract::Previous studies have established the in vivo bioavailability and efficacious dosages of phenylbutyl isoselenocyanate (ISC-4), a selenium-substituted isothiocyanate, against mouse xenograft models of human melanoma and colorectal cancer. To explore its potential attributes against prostate cancer, we treated human LNC...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22825

    authors: Wu W,Karelia D,Pramanik K,Amin SG,Sharma AK,Jiang C,Lu J

    更新日期:2018-08-01 00:00:00

  • Dys-regulation of clusterin in human hepatoma is not associated with tumorigenesis but is secondary to cell response to external tresses.

    abstract::It becomes feasible to perform genome-wide differential gene or protein expression in the post genome era. However, little has been addressed on the effects of external stresses and microenvironment alterations on the outcomes of gene and protein expression. To identify downregulated genes during hepatoma development,...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20095

    authors: Hsieh SY,Chen WY,Shih TC,Yeh JY,Jeng JT

    更新日期:2005-06-01 00:00:00

  • Reduction in transforming growth factor-beta type II receptor in mouse lung carcinogenesis.

    abstract::Transforming growth factor-beta (TGF-beta) is a growth modulator that inhibits the proliferation of many epithelial cells through interaction with its receptors, the type I and type II receptors (TGF-beta RI and RII) by activating their serine/threonine kinase activities. Loss of growth inhibition by TGF-beta is thoug...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/(sici)1098-2744(199805)22:1<46::aid-mc6>3.

    authors: Jakowlew SB,Moody TW,You L,Mariano JM

    更新日期:1998-05-01 00:00:00

  • Effect of energy restriction on the expression of cyclin D1 and p27 during premalignant and malignant stages of chemically induced mammary carcinogenesis.

    abstract::The restriction of energy intake has a profound inhibitory effect on carcinogenesis, yet the mechanism or mechanisms that account for this effect are unknown. In this experiment, the hypothesis tested was that energy restriction upregulates the expression of p27/kip1, a gene product associated with cell-cycle growth a...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/(sici)1098-2744(199904)24:4<241::aid-mc1>3

    authors: Zhu Z,Jiang W,Thompson HJ

    更新日期:1999-04-01 00:00:00

  • bcl-2 delay of alkylating agent-induced apoptotic death in a murine hemopoietic stem cell line.

    abstract::Many cytotoxic agents kill cells by invoking a specific death pathway termed physiological cell death, or apoptosis. Treatment of a murine hemopoietic stem cell line, FDCP-mix, with methylmethanesulfonate (MMS) or N'-methyl-N'-nitrosourea (MNU) leads to death by apoptosis. Retroviral gene transfer was used to overexpr...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.2940110109

    authors: Fairbairn LJ,Cowling GJ,Dexter TM,Rafferty JA,Margison GP,Reipert B

    更新日期:1994-09-01 00:00:00

  • Identification of RB and p53 mutations in mouse lymphoma cell lines.

    abstract::We analyzed the genomic structure and mRNA of the RB and p53 genes in four mouse lymphoid leukemia cell lines (DL-1, DL-5, DL-8, and DL-12). Although no gross structural alteration of the RB gene was observed in any cell line, abnormalities of RB mRNA were detected in at least two cell lines. RB mRNA expression was gr...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.2940040505

    authors: Murakami A,Tanaka H

    更新日期:1991-01-01 00:00:00

  • Nicotinamide N-methyltransferase decreases 5-fluorouracil sensitivity in human esophageal squamous cell carcinoma through metabolic reprogramming and promoting the Warburg effect.

    abstract::Esophageal squamous cell carcinoma (ESCC) is a common malignant tumor with poor prognosis. And different individuals respond to the same drug differently. Increasing evidence has confirmed that metabolism reprogramming was involved in the drug sensitivity of tumor cells. However, the potential molecular mechanism of 5...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.23209

    authors: Cui Y,Yang D,Wang W,Zhang L,Liu H,Ma S,Guo W,Yao M,Zhang K,Li W,Zhang Y,Guan F

    更新日期:2020-08-01 00:00:00

  • 2-methoxyestradiol blocks cell-cycle progression at G(2)/M phase and inhibits growth of human prostate cancer cells.

    abstract::2-Methoxyestradiol (2-ME), an endogenous metabolite of 17beta-estradiol, is present in human blood and urine. Here we show for the first time that 2-ME significantly inhibited the growth of normal prostate epithelial cells and androgen-dependent LNCaP and androgen-independent DU145 prostate cancer cells. This growth i...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.1046

    authors: Kumar AP,Garcia GE,Slaga TJ

    更新日期:2001-07-01 00:00:00

  • BCL2L10 inhibits growth and metastasis of hepatocellular carcinoma both in vitro and in vivo.

    abstract::BCL2L10 is an apoptosis-related member of the BCL-2 protein family. The role of BCL2L10 in the pathogenesis of hepatocellular carcinoma (HCC) is poorly understood. This study was aimed to investigate the function and underlying mechanisms of BCL2L10 in HCC. BCL2L10 expression in human HCC and corresponding adjacent no...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22580

    authors: Bai Y,Wang J,Han J,Xie XL,Ji CG,Yin J,Chen L,Wang CK,Jiang XY,Qi W,Jiang HQ

    更新日期:2017-03-01 00:00:00

  • Requirement of wild-type p53 protein for maintenance of chromosomal integrity.

    abstract::Chromosomal double-strand breaks (DSBs) occurring in mammalian cells can initiate genomic instability, and their misrepairs result in chromosomal deletion, amplification, and translocation, common findings in human tumors. The tumor-suppressor protein p53 is involved in maintaining genomic stability. In this study, we...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/1098-2744(200008)28:4<203::aid-mc3>3.0.co;

    authors: Honma M,Momose M,Tanabe H,Sakamoto H,Yu Y,Little JB,Sofuni T,Hayashi M

    更新日期:2000-08-01 00:00:00

  • Differential expression of the O6-alkylguanine-DNA alkyltransferase gene in normal human breast and skin tissue: in situ mapping of cell type-specific expression.

    abstract::O6-Alkylguanine is a major toxic, mutagenic, and carcinogenic lesion in cellular DNA that is repaired by O6-alkylguanine-DNA alkyltransferase (ATase). The expression of this gene is directly related to the cellular sensitivity of alkylating agents, with levels of this protein varying widely among human organs, tumors,...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.2940120309

    authors: Wani G,D'Ambrosio SM

    更新日期:1995-03-01 00:00:00

  • Induction of the mesenchymal to epithelial transition by demethylation- activated microRNA-200c is involved in the anti-migration/invasion effects of arsenic trioxide on human breast cancer cells.

    abstract::Breast cancer is a major health problem worldwide. Current standard practices for treatment of breast cancer are less than satisfactory because of high rates of metastasis. Arsenic trioxide (As(2)O(3)), which induces demethylation of DNA and causes apoptosis, has been used as an anti-tumor agent. Little is known, howe...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22157

    authors: Si L,Jiang F,Li Y,Ye X,Mu J,Wang X,Ning S,Hu C,Li Z

    更新日期:2015-09-01 00:00:00

  • Association of the EGFR intron 1 CA repeat length with lung cancer risk.

    abstract::Epidermal growth factor receptor (EGFR) plays an important role in the development and progression of lung cancer. A previous report noted that an increased number of polymorphic CA repeats in the first intron of the EGFR gene results in decreased transcriptional activity. To estimate the association of the length of ...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20285

    authors: Zhang W,Weissfeld JL,Romkes M,Land SR,Grandis JR,Siegfried JM

    更新日期:2007-05-01 00:00:00