LIVIVO - Search results -

Search results

Result 1 - 10 of total 34

Search options

Article ; Online: AP4 induces JNK1 and a miR-22-3p/FOSL1 feed-forward loop to activate AP-1 and promote colorectal cancer metastasis.

Chou, Jinjiang / Kaller, Markus / Rokavec, Matjaz / Liu, Fangteng / Hermeking, Heiko

Cancer communications (London, England)

2024 Volume 44, Issue 3, Page(s) 433–437

MeSH term(s)	Humans ; Transcription Factor AP-1 ; MicroRNAs/genetics ; Colorectal Neoplasms/pathology
Chemical Substances	Transcription Factor AP-1 ; MicroRNAs ; MIRN22 microRNA, human
Language	English
Publishing date	2024-01-15
Publishing country	United States
Document type	Letter
ISSN	2523-3548
ISSN (online)	2523-3548
DOI	10.1002/cac2.12514
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article: Nidogen-1/NID1 Function and Regulation during Progression and Metastasis of Colorectal Cancer.

Rokavec, Matjaz / Jaeckel, Stephanie / Hermeking, Heiko

Cancers

2023 Volume 15, Issue 22

Abstract: We have previously shown that the extracellular matrix and basement membrane protein Nidogen1 (NID1) is secreted by more malignant, mesenchymal-like CRC cells and induces the epithelial-mesenchymal transition (EMT) and promotes the migration and invasion ...

Abstract	We have previously shown that the extracellular matrix and basement membrane protein Nidogen1 (NID1) is secreted by more malignant, mesenchymal-like CRC cells and induces the epithelial-mesenchymal transition (EMT) and promotes the migration and invasion of less malignant, epithelial-like CRC cells. Here, we performed a comprehensive bioinformatics analysis of multiple datasets derived from CRC patients and showed that elevated expression of
Language	English
Publishing date	2023-11-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15225316
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Squalene epoxidase/SQLE is a candidate target for treatment of colorectal cancers with

Du, Yuyun / Rokavec, Matjaz / Hermeking, Heiko

International journal of biological sciences

2023 Volume 19, Issue 13, Page(s) 4103–4122

Abstract: Elevated expression of c-MYC and inactivation ... ...

Abstract	Elevated expression of c-MYC and inactivation of
MeSH term(s)	Humans ; Squalene Monooxygenase/genetics ; Tumor Suppressor Protein p53/genetics ; Mutation ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/genetics ; Cholesterol
Chemical Substances	Squalene Monooxygenase (EC 1.14.14.17) ; Tumor Suppressor Protein p53 ; Cholesterol (97C5T2UQ7J)
Language	English
Publishing date	2023-08-06
Publishing country	Australia
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2179208-2
ISSN	1449-2288 ; 1449-2288
ISSN (online)	1449-2288
ISSN	1449-2288
DOI	10.7150/ijbs.85724
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Development and Validation of a 15-gene Expression Signature with Superior Prognostic Ability in Stage II Colorectal Cancer.

Rokavec, Matjaz / Özcan, Elif / Neumann, Jens / Hermeking, Heiko

Cancer research communications

2023 Volume 3, Issue 8, Page(s) 1689–1700

Abstract: Currently, there is no consensus about the use of adjuvant chemotherapy for patients with stage II colorectal cancer. Here, we aimed to identify and validate a prognostic mRNA expression signature for the stratification of patients with stage II ... ...

Abstract	Currently, there is no consensus about the use of adjuvant chemotherapy for patients with stage II colorectal cancer. Here, we aimed to identify and validate a prognostic mRNA expression signature for the stratification of patients with stage II colorectal cancer according to their risk for relapse. First, publicly available mRNA expression profiling datasets from 792 primary, stage II colorectal cancers from six different training cohorts were analyzed to identify genes that are consistently associated with patient relapse-free survival (RFS). Second, the identified gene expression signature was experimentally validated using NanoString technology and computationally refined on primary colorectal cancer samples from 205 patients with stage II colorectal cancer. Third, the refined signature was validated in two independent publicly available cohorts of 166 patients with stage II colorectal cancer. Bioinformatics analysis of training cohorts identified a 61-gene signature that was highly significantly associated with RFS (HR = 37.08, Significance: We identified and validated a 15-gene expression signature for robust prognostication and stratification of patients with stage II colorectal cancer, with superior performance when compared with currently used biomarkers. Therefore, the 15-gene expression signature has the potential to improve the prognostication and treatment decisions for patients with stage II colorectal cancer.
MeSH term(s)	Humans ; Prognosis ; Transcriptome/genetics ; Colorectal Neoplasms/genetics ; RNA, Messenger
Chemical Substances	RNA, Messenger
Language	English
Publishing date	2023-08-30
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2767-9764
ISSN (online)	2767-9764
DOI	10.1158/2767-9764.CRC-22-0489
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Salicylate induces AMPK and inhibits c-MYC to activate a NRF2/ARE/miR-34a/b/c cascade resulting in suppression of colorectal cancer metastasis.

Liu, Chunfeng / Rokavec, Matjaz / Huang, Zekai / Hermeking, Heiko

Cell death & disease

2023 Volume 14, Issue 10, Page(s) 707

Abstract: Aspirin and its active metabolite salicylate have emerged as promising agents for the chemoprevention of colorectal cancer (CRC). Moreover, aspirin suppresses the progression of established CRCs. However, the underlying molecular mechanisms are not ... ...

Abstract	Aspirin and its active metabolite salicylate have emerged as promising agents for the chemoprevention of colorectal cancer (CRC). Moreover, aspirin suppresses the progression of established CRCs. However, the underlying molecular mechanisms are not completely understood. Here we found that salicylate induces the expression of the miR-34a and miR-34b/c genes, which encode tumor suppressive microRNAs, in a p53-independent manner. Salicylate activated AMPK, thereby activating NRF2, which directly induced miR-34a/b/c expression via ARE motifs. In addition, salicylate suppressed c-MYC, a known repressor of NRF2-mediated transactivation, via activating AMPK. The suppression of c-MYC by salicylate was necessary for NRF2-mediated activation of miR-34a/b/c. Inactivation of miR-34a/b/c largely abrogated the inhibitory effects of salicylate on migration, invasion and metastasis formation by CRC cells. In the future, aspirin and its derivates may be used therapeutically to activate miR-34a and miR-34b/c in tumors that have lost p53.
MeSH term(s)	Humans ; AMP-Activated Protein Kinases/metabolism ; NF-E2-Related Factor 2/genetics ; NF-E2-Related Factor 2/metabolism ; Tumor Suppressor Protein p53/genetics ; Tumor Suppressor Protein p53/metabolism ; Salicylates/pharmacology ; Cell Line, Tumor ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/metabolism ; Aspirin/pharmacology ; Gene Expression Regulation, Neoplastic
Chemical Substances	AMP-Activated Protein Kinases (EC 2.7.11.31) ; NF-E2-Related Factor 2 ; Tumor Suppressor Protein p53 ; Salicylates ; MicroRNAs ; Aspirin (R16CO5Y76E)
Language	English
Publishing date	2023-10-28
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2541626-1
ISSN	2041-4889 ; 2041-4889
ISSN (online)	2041-4889
ISSN	2041-4889
DOI	10.1038/s41419-023-06226-9
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Curcumin activates a ROS/KEAP1/NRF2/miR-34a/b/c cascade to suppress colorectal cancer metastasis.

Liu, Chunfeng / Rokavec, Matjaz / Huang, Zekai / Hermeking, Heiko

Cell death and differentiation

2023 Volume 30, Issue 7, Page(s) 1771–1785

Abstract: Curcumin, a natural phytochemical isolated from tumeric roots, represents a candidate for prevention and therapy of colorectal cancer/CRC. However, the exact mechanism of action and the downstream mediators of curcumin's tumor suppressive effects have ... ...

Abstract	Curcumin, a natural phytochemical isolated from tumeric roots, represents a candidate for prevention and therapy of colorectal cancer/CRC. However, the exact mechanism of action and the downstream mediators of curcumin's tumor suppressive effects have remained largely unknown. Here we used a genetic approach to determine the role of the p53/miR-34 pathway as mediator of the effects of curcumin. Three isogenic CRC cell lines rendered deficient for the p53, miR-34a and/or miR-34b/c genes were exposed to curcumin and subjected to cell biological analyses. siRNA-mediated inhibition and ectopic expression of NRF2, as well as Western blot, qPCR and qChIP analyses of its target genes were performed. CRC cells were i.v. injected into NOD/SCID mice and lung-metastases formation was determined by longitudinal, non-invasive imaging. In CRC cells curcumin induced apoptosis and senescence, and suppressed migration and invasion in a p53-independent manner. Curcumin activated the KEAP1/NRF2/ARE pathway by inducing ROS. Notably, curcumin induced miR-34a and miR-34b/c expression in a ROS/NRF2-dependent and p53-independent manner. NRF2 directly induced miR-34a and miR-34b/c via occupying multiple ARE motifs in their promoter regions. Curcumin reverted repression of miR-34a and miR-34b/c induced by IL6 and hypoxia. Deletion of miR-34a and miR-34b/c significantly reduced curcumin-induced apoptosis and senescence, and prevented the inhibition of migration and invasion by curcumin or ectopic NRF2. In CRC cells curcumin induced MET and prevented the formation of lung-metastases in mice in a miR-34a-dependent manner. In addition, we found that curcumin may enhance the therapeutic effects of 5-FU on CRC cells deficient for p53 and miR-34a/b/c. Activation of the KEAP1/NRF2/miR-34a/b/c axis mediates the tumor suppressive activity of curcumin and suggests a new approach for activating miR-34 genes in tumors for therapeutic purposes.
MeSH term(s)	Animals ; Mice ; Cell Line, Tumor ; Colorectal Neoplasms/metabolism ; Colorectal Neoplasms/therapy ; Curcumin/pharmacology ; Gene Expression Regulation, Neoplastic ; Kelch-Like ECH-Associated Protein 1/metabolism ; Lung Neoplasms/secondary ; Lung Neoplasms/therapy ; Mice, Inbred NOD ; Mice, SCID ; MicroRNAs ; NF-E2-Related Factor 2/metabolism ; Reactive Oxygen Species/metabolism ; Tumor Suppressor Protein p53/metabolism
Chemical Substances	Curcumin (IT942ZTH98) ; Kelch-Like ECH-Associated Protein 1 ; MicroRNAs ; NF-E2-Related Factor 2 ; Reactive Oxygen Species ; Tumor Suppressor Protein p53
Language	English
Publishing date	2023-05-20
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1225672-9
ISSN	1476-5403 ; 1350-9047
ISSN (online)	1476-5403
ISSN	1350-9047
DOI	10.1038/s41418-023-01178-1
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 4230: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 80: Show issues

Order via subito

Details ▾

Article: miR-34a and IRE1A/XBP-1(S) Form a Double-Negative Feedback Loop to Regulate Hypoxia-Induced EMT, Metastasis, Chemo-Resistance and Autophagy.

Bouznad, Nassim / Rokavec, Matjaz / Öner, Meryem Gülfem / Hermeking, Heiko

Cancers

2023 Volume 15, Issue 4

Abstract: Tumor-associated hypoxia, i.e., decreased availability of oxygen, results in a poor clinical outcome since it promotes EMT, metastasis, and chemotherapy-resistance. We have previously identified p53 and its target miR-34a, as critical determinants of the ...

Abstract	Tumor-associated hypoxia, i.e., decreased availability of oxygen, results in a poor clinical outcome since it promotes EMT, metastasis, and chemotherapy-resistance. We have previously identified p53 and its target miR-34a, as critical determinants of the effect of hypoxia on colorectal cancer (CRC). Here, we aimed to characterize mechanisms that contribute to the selective advantage of cells with loss of p53/miR-34a function in a hypoxic environment. Using in silico prediction, we identified XBP-1 and IRE1A as potential miR-34a targets. IRE1A and XBP-1 are central components of the unfolded protein response that is activated by ER stress, which is also induced in tumor cells as a response to harsh conditions surrounding tumors such as hypoxia and a limited supply of nutrients. Here we characterized the XBP-1(S) transcription factor and its regulator IRE1A as direct, conserved miR-34a targets in CRC cells. After hypoxia and DNA damage, IRE1A and XBP-1 were repressed by p53 in a miR-34a-dependent manner, whereas
Language	English
Publishing date	2023-02-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15041143
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article: Meta-analysis of miR-34 target mRNAs using an integrative online application.

Rokavec, Matjaz / Huang, Zekai / Hermeking, Heiko

Computational and structural biotechnology journal

2022 Volume 21, Page(s) 267–274

Abstract: Members of the microRNA-34/miR-34 family are induced by the p53 tumor suppressor and themselves possess tumor suppressive properties, as they inhibit the translation of mRNAs that encode proteins involved in processes, such as proliferation, migration, ... ...

Abstract	Members of the microRNA-34/miR-34 family are induced by the p53 tumor suppressor and themselves possess tumor suppressive properties, as they inhibit the translation of mRNAs that encode proteins involved in processes, such as proliferation, migration, invasion, and metastasis. Here we performed a comprehensive integrative meta-analysis of multiple computational and experimental miR-34 related datasets and developed tools to identify and characterize novel miR-34 targets. A miR-34 target probability score was generated for every mRNA to estimate the likelihood of representing a miR-34 target. Experimentally validated miR-34 targets were strongly enriched among mRNAs with the highest scores providing a proof of principle for our analysis. We integrated the results from the meta-analysis in a user-friendly METAmiR34TARGET website (www.metamir34target.com/) that allows to graphically represent the meta-analysis results for every mRNA. Moreover, the website harbors a screen function, which allows to select multiple miR-34-related criteria/analyses and cut-off values to facilitate the stringent and comprehensive prediction of relevant miR-34 targets in expression data obtained from cell lines and tumors/tissues. Furthermore, information on more than 200 miR-34 target mRNAs, that have been experimentally validated so far, has been integrated in the web-tool. The website and datasets provided here should facilitate further investigation into the mechanisms of tumor suppression by the p53/miR-34 connection and identification of potential cancer drug targets.
Language	English
Publishing date	2022-12-06
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2694435-2
ISSN	2001-0370
ISSN	2001-0370
DOI	10.1016/j.csbj.2022.12.003
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: AP4 suppresses DNA damage, chromosomal instability and senescence via inducing MDC1/Mediator of DNA damage Checkpoint 1 and repressing MIR22HG/miR-22-3p.

Chou, Jinjiang / Kaller, Markus / Jaeckel, Stephanie / Rokavec, Matjaz / Hermeking, Heiko

Molecular cancer

2022 Volume 21, Issue 1, Page(s) 120

Abstract: Background: AP4 (TFAP4) encodes a basic helix-loop-helix leucine zipper (bHLH-LZ) transcription factor and is a direct target gene of the oncogenic transcription factor c-MYC. Here, we set out to determine the relevance of AP4 in human colorectal cancer ...

Abstract	Background: AP4 (TFAP4) encodes a basic helix-loop-helix leucine zipper (bHLH-LZ) transcription factor and is a direct target gene of the oncogenic transcription factor c-MYC. Here, we set out to determine the relevance of AP4 in human colorectal cancer (CRC) cells. Methods: A CRISPR/Cas9 approach was employed to generate AP4-deficient CRC cell lines with inducible expression of c-MYC. Colony formation, β-gal staining, immunofluorescence, comet and homologous recombination (HR) assays and RNA-Seq analysis were used to determine the effects of AP4 inactivation. qPCR and qChIP analyses was performed to validate differentially expressed AP4 targets. Expression data from CRC cohorts was subjected to bioinformatics analyses. Immunohistochemistry was used to evaluate AP4 targets in vivo. Ap4-deficient APC Results: Inactivation of AP4 in CRC cell lines resulted in increased spontaneous and c-MYC-induced DNA damage, chromosomal instability (CIN) and cellular senescence. AP4-deficient cells displayed increased expression of the long non-coding RNA MIR22HG, which encodes miR-22-3p and was directly repressed by AP4. Furthermore, Mediator of DNA damage Checkpoint 1 (MDC1), a central component of the DNA damage response and a known target of miR-22-3p, displayed decreased expression in AP4-deficient cells. Accordingly, MDC1 was directly induced by AP4 and indirectly by AP4-mediated repression of miR-22-3p. Adenomas and organoids from Ap4-deficient APC Conclusions: In summary, AP4, miR-22-3p and MDC1 form a conserved and coherent, regulatory feed-forward loop to promote DNA repair, which suppresses DNA damage, senescence and CIN, and contributes to 5-FU resistance. These findings explain how elevated AP4 expression contributes to development and chemo-resistance of colorectal cancer after c-MYC activation.
MeSH term(s)	Adaptor Proteins, Signal Transducing/genetics ; Animals ; Cell Cycle Proteins/genetics ; Chromosomal Instability ; Colorectal Neoplasms/genetics ; DNA Damage ; Fluorouracil/pharmacology ; Gene Expression Regulation, Neoplastic ; Humans ; Mice ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Transcription Factors/genetics
Chemical Substances	Adaptor Proteins, Signal Transducing ; Cell Cycle Proteins ; MDC1 protein, human ; MIRN22 microRNA, human ; MicroRNAs ; Transcription Factors ; Fluorouracil (U3P01618RT)
Language	English
Publishing date	2022-05-27
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2091373-4
ISSN	1476-4598 ; 1476-4598
ISSN (online)	1476-4598
ISSN	1476-4598
DOI	10.1186/s12943-022-01581-1
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: 14-3-3σ

Winter, Markus / Rokavec, Matjaž / Hermeking, Heiko

Cancer research

2021 Volume 81, Issue 13, Page(s) 3621–3634

Abstract: ... Although ... ...

Abstract	Although the
MeSH term(s)	14-3-3 Proteins/genetics ; 14-3-3 Proteins/metabolism ; Animals ; Apoptosis ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; Carcinogenesis/genetics ; Carcinogenesis/metabolism ; Carcinogenesis/pathology ; Cell Proliferation ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/metabolism ; Colorectal Neoplasms/pathology ; Epithelial-Mesenchymal Transition ; Exoribonucleases/genetics ; Exoribonucleases/metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Genes, APC ; Genes, Tumor Suppressor ; Intestinal Mucosa/metabolism ; Intestinal Mucosa/pathology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Prognosis ; Survival Rate ; Tumor Cells, Cultured
Chemical Substances	14-3-3 Proteins ; Biomarkers, Tumor ; Exoribonucleases (EC 3.1.-) ; SFN protein, human (EC 3.1.-)
Language	English
Publishing date	2021-06-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1432-1
ISSN	1538-7445 ; 0008-5472
ISSN (online)	1538-7445
ISSN	0008-5472
DOI	10.1158/0008-5472.CAN-20-4192
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Uh III Zs.135/5: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

To top

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito