Publications by authors named "Żaneta Kałuzińska"

5 Publications

  • Page 1 of 1

Fragile Gene Guides /-Dependent Actions Against Tumor Progression in Grade II Bladder Cancer.

Front Oncol 2021 25;11:621060. Epub 2021 Feb 25.

Department of Molecular Carcinogenesis, Medical University of Lodz, Łódź, Poland.

Introduction: The presence of common fragile sites is associated with no-accidental chromosomal instability which occurs prior to carcinogenesis. The gene spans the second most active fragile site: FRA16D. Chromosomal breakage at this site is more common in bladder cancer patients who are tobacco smokers which suggests the importance of gene loss regarding bladder carcinogenesis. Tryptophan domains of WWOX are known to recognize motifs of other proteins such as AP-2α and AP-2γ allowing protein-protein interactions. While the roles of both AP-2 transcription factors are important for bladder carcinogenesis, their nature is different. Based on the literature, AP-2γ appears to be oncogenic, whereas AP-2α mainly exhibits tumor suppressor character. Presumably, the interaction between WWOX and both transcription factors regulates thousands of genes, hence the aim of the present study was to determine WWOX, AP-2α, and AP-2γ function in modulating biological processes of bladder cancer.

Methods: RT-112 cell line (grade II bladder cancer) was subjected to two stable lentiviral transductions. Overall, this resulted in six variants to investigate distinct WWOX, AP-2α, or AP-2γ function as well as WWOX in collaboration with a particular transcription factor. Cellular models were examined with immunocytochemical staining and in terms of differences in biological processes using assays investigating cell viability, proliferation, apoptosis, adhesion, clonogenicity, migration, activity of metalloproteinases and 3D culture growth.

Results: WWOX overexpression increased apoptosis but decreased cell viability, migration and large spatial colonies. AP-2α overexpression decreased tumor cell viability, migratory potential, matrix metalloproteinase-2 activity and clonogenicity. AP-2γ overexpression decreased matrix metalloproteinase-2 activity but increased wound healing, adhesion, clonogenicity and spatial colony formation. WWOX and AP-2α overexpression induced apoptosis but decreased cell viability, adhesion, matrix metalloproteinase-2 activity, overall number of cultured colonies and migration rate. WWOX and AP-2γ overexpression decreased tumor cell viability, proliferation potential, adhesion, clonogenicity and the ability to create spatial structures, but also increased apoptosis or migration rate.

Conclusion: Co-overexpression of WWOX with AP-2α or WWOX with AP-2γ resulted in a net anti-tumor effect. However, considering this research findings and the difference between AP-2α and AP-2γ, we suggest that this similarity is due to a divergent behavior of WWOX.
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http://dx.doi.org/10.3389/fonc.2021.621060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947623PMC
February 2021

In vitro and in silico assessment of the effect of WWOX expression on invasiveness pathways associated with AP-2 transcription factors in bladder cancer.

BMC Urol 2021 Mar 10;21(1):36. Epub 2021 Mar 10.

Department of Molecular Carcinogenesis, Medical University of Lodz, 90-752, Lodz, Poland.

Background: WW Domain Containing Oxidoreductase (WWOX) belongs to the unusual tumor suppressors, whose molecular function is not fully understood in bladder cancer, especially regarding interaction with Activator Protein 2 (AP-2) α/γ transcription factors. Thus, using lentiviral systems we created an in vitro model overexpressing or downregulating WWOX in CAL-29 cell line to assess invasiveness pathways. Surprisingly, while WWOX overexpression was accompanied with increased expression of both AP-2 factors, its downregulation only affected AP-2α level but not AP-2γ which remained high.

Methods: Using cellular models and unpaired t-test or Wilcoxon test, we investigated significant changes in biological processes: clonogenicity, extracellular matrix adhesion, metalloproteinases activity, 3D culture growth, proliferation, mitochondrial redox potential and invasiveness. Relative gene expression acquired through Real-Time qPCR has been analyzed by Welch's t-test. Additionally, using oncoprint analysis we distinguished groups for bioinformatics analyzes in order to perform a follow-up of in vitro experiments.

Results: Downregulation of WWOX in bladder cancer cell line intensified ability of single cell to grow into colony, mitochondrial redox potential and proliferation rate. Moreover, these cells shown elevated pro-MMP-2/9 activity but reduced adhesion to collagen I or laminin I, as well as distinct 3D culture growth. Through global in silico profiling we determined that WWOX alters disease-free survival of bladder cancer patients and modulates vital processes through AP-2 downstream effectors.

Conclusions: Our research indicates that WWOX possesses tumor suppressor properties in bladder cancer but consecutive examination is required to entirely understand the contribution of AP-2γ or AP-2α.
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http://dx.doi.org/10.1186/s12894-021-00806-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944886PMC
March 2021

MicroRNAs: Their Role in Metastasis, Angiogenesis, and the Potential for Biomarker Utility in Bladder Carcinomas.

Cancers (Basel) 2021 Feb 20;13(4). Epub 2021 Feb 20.

Department of Molecular Carcinogenesis, Medical University of Lodz, Zeligowskiego 7/9, 90-752 Lodz, Poland.

Angiogenesis is the process of generating new capillaries from pre-existing blood vessels with a vital role in tumor growth and metastasis. MicroRNAs (miRNAs) are noncoding RNAs that exert post-transcriptional control of protein regulation. They participate in the development and progression of several cancers including bladder cancer (BLCA). In cancer tissue, changes in microRNA expression exhibit tissue specificity with high levels of stability and detectability. miRNAs are less vulnerable to degradation, making them novel targets for therapeutic approaches. A suitable means of targeting aberrant activated signal transduction pathways in carcinogenesis of BLCA is possibly through altering the expression of key miRNAs that regulate them, exerting a strong effect on signal transduction. Precaution must be taken, as the complexity of miRNA regulation might result in targeting several downstream tumor suppressors or oncogenes, enhancing the effect further. Since exosomes contain both mRNA and miRNA, they could therefore possibly be more effective in targeting a recipient cell if they deliver a specific miRNA to modify the recipient cell protein production and gene expression. In this review, we discuss the molecules that have been shown to play a significant role in BLCA tumor development. We also discuss the roles of various miRNAs in BLCA angiogenesis and metastasis. Advances in the management of metastatic BLCA have been limited; miRNA mimics and molecules targeted at miRNAs (anti-miRs) as well as exosomes could serve as therapeutic modalities or as diagnostic biomarkers.
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http://dx.doi.org/10.3390/cancers13040891DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924383PMC
February 2021

Functional genomics of AP-2α and AP-2γ in cancers: in silico study.

BMC Med Genomics 2020 11 19;13(1):174. Epub 2020 Nov 19.

Department of Molecular Carcinogenesis, Medical University of Lodz, 90-752, Lodz, Poland.

Background: Among all causes of death, cancer is the most prevalent and is only outpaced by cardiovascular diseases. Molecular theory of carcinogenesis states that apoptosis and proliferation are regulated by groups of tumor suppressors or oncogenes. Transcription factors are example of proteins comprising representatives of both cancer-related groups. Exemplary family of transcription factors which exhibits dualism of function is Activating enhancer-binding Protein 2 (AP-2). Scientific reports concerning their function in carcinogenesis depend on particular family member and/or tumor type which proves the issue to be unsolved. Therefore, the present study examines role of the best-described AP-2 representatives, AP-2α and AP-2γ, through ontological analysis of their target genes and investigation what processes are differentially regulated in 21 cancers using samples deposited in Genomic Data Analysis Center (GDAC) Firehose.

Methods: Expression data with clinical annotation was collected from TCGA-dedicated repository GDAC Firehose. Transcription factor targets were obtained from Gene Transcription Regulation Database (GTRD), TRANScription FACtor database (TRANSFAC) and Transcriptional Regulatory Relationships Unraveled by Sentence-based Text mining (TRRUST). Monocle3 R package was used for global samples profiling while Protein ANalysis THrough Evolutionary Relationships (PANTHER) tool was used to perform gene ontology analysis.

Results: With RNA-seq data and Monocle3 or PANTHER tools we outlined differences in many processes and signaling pathways, separating tumor from normal tissues or tumors from each other. Unexpectedly, a number of alterations in basal-like breast cancer were identified that distinguished it from other subtypes, which could bring future clinical benefits.

Conclusions: Our findings indicate that while the AP-2α/γ role remains ambiguous, their activity is based on processes that underlie the cancer hallmarks and their expression could have potential in diagnosis of selected tumors.
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http://dx.doi.org/10.1186/s12920-020-00823-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678100PMC
November 2020

The biological characteristics of transcription factors AP-2α and AP-2γ and their importance in various types of cancers.

Biosci Rep 2019 03 15;39(3). Epub 2019 Mar 15.

Department of Molecular Carcinogenesis, Medical University of Lodz, Lodz, Poland

The Activator Protein 2 (AP-2) transcription factor (TF) family is vital for the regulation of gene expression during early development as well as carcinogenesis process. The review focusses on the AP-2α and AP-2γ proteins and their dualistic regulation of gene expression in the process of carcinogenesis. Both AP-2α and AP-2γ influence a wide range of physiological or pathological processes by regulating different pathways and interacting with diverse molecules, i.e. other proteins, long non-coding RNAs (lncRNA) or miRNAs. This review summarizes the newest information about the biology of two, AP-2α and AP-2γ, TFs in the carcinogenesis process. We emphasize that these two proteins could have either oncogenic or suppressive characteristics depending on the type of cancer tissue or their interaction with specific molecules. They have also been found to contribute to resistance and sensitivity to chemotherapy in oncological patients. A better understanding of molecular network of AP-2 factors and other molecules may clarify the atypical molecular mechanisms occurring during carcinogenesis, and may assist in the recognition of new diagnostic biomarkers.
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http://dx.doi.org/10.1042/BSR20181928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6418405PMC
March 2019