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The Role of Genotoxicity in Infertility and Cancer Development

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A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Molecular Genetics and Genomics".

Deadline for manuscript submissions: closed (22 November 2019) | Viewed by 31423

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Special Issue Editors

Dr. Kavindra K. Kesari

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Guest Editor

Department of Applied Physics, Aalto University, Espoo 00076, Finland
Interests: testicular cancer; infertility; Alzheimer’s disease; cancer therapeutic; neurotoxicity; brain cancer; nanoparticle research; radiation research; bioinformatics; cell and structural biology
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Dhruv Kumar

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Amity Institute of Molecular Medicine & Stem Cell Research (AIMMSCR), Amity University Uttar Pradesh, Sec-125, Noida 201313, India
Interests: autophagy; bioinformatics; cancer prevention; cancer therapeutics; cancer genomics; cancer proteomics; cancer stem cell; cancer metabolism; drug discovery; tumor-microenvironment; translational cancer research
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Janne Ruokolainen

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Guest Editor

Department of Applied Physics, School of Science, Aalto University, Espoo, Finland
Interests: transmission electron microscopy; scanning electron microscopy; genotoxicity; cancer therapeutic; neurotoxicity; nanoparticle research; cell and structural biology; molecular materials; nanocellulose; biocomputation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Day after day, every individual is exposed to different chemicals and particles that react with our genetic material, causing myriad consequences for our health and routine. Global industrialization together with the development of our health system has led to an exponential growth in the number of toxics we use for different matters. Innovative/systemic therapies widely used for different treatments are based on the use of genotoxics that directly influence the growth of our cells. Not only that, but genotoxicity is one of the principal factors to induce cancer and infertility in humans, mainly caused by radiation and chemicals, which can cause DNA damage and induce mutations and chromosomal rearrangements. The derived toxicity of genotoxics in somatic cells in the form of DNA damage may lead to the development of cancer and aberrations in germline cells, which can lead to the development of several genetic disorders and infertility. Therefore, a better understanding of the molecular mechanisms related with genotoxicity and its regulation in cancer and infertility will help us understand how to develop potential therapeutic and preventive approaches.

In this Special Issue, our aim is to collect a series of research articles and reviews from a diverse group of the scientific community to share their research work on the role of genotoxicity in cancer and infertility development, which will provide readers with a better understanding of genotoxicity in cancer and infertility.

If you decide to submit your manuscript to the issue before September 10 2019 you will receive a 30% discount on the Article Processing Charges (APC).

Kind regards,

Dr. Kavindra Kumar Kesari
Prof. Dhruv Kumar
Prof. Janne Ruokolainen
Guest Editors

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Genes is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

genotoxicity
infertility
DNA damage
cancer
mutagens
nano-toxicity

Published Papers (6 papers)

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Research

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19 pages, 2536 KiB

Open AccessArticle

Transcriptome Meta-Analysis Deciphers a Dysregulation in Immune Response-Associated Gene Signatures during Sepsis

by Shaniya Ahmad, Prithvi Singh, Archana Sharma, Shweta Arora, Nitesh Shriwash, Arshad Husain Rahmani, Saleh A. Almatroodi, Kailash Manda, Ravins Dohare and Mansoor Ali Syed

Genes 2019, 10(12), 1005; https://0-doi-org.brum.beds.ac.uk/10.3390/genes10121005 - 04 Dec 2019

Cited by 24 | Viewed by 5390

Abstract

Sepsis is a life-threatening disease induced by a systemic inflammatory response, which leads to organ dysfunction and mortality. In sepsis, the host immune response is depressed and unable to cope with infection; no drug is currently available to treat this. The lungs are frequently the starting point for sepsis. This study aimed to identify potential genes for diagnostics and therapeutic purposes in sepsis by a comprehensive bioinformatics analysis. Our criteria are to unravel sepsis-associated signature genes from gene expression datasets. Differentially expressed genes (DEGs) were identified from samples of sepsis patients using a meta-analysis and then further subjected to functional enrichment and protein‒protein interaction (PPI) network analysis for examining their potential functions. Finally, the expression of the topmost upregulated genes (ARG1, IL1R2, ELANE, MMP9) was quantified by reverse transcriptase-PCR (RT-PCR), and myeloperoxidase (MPO) expression was confirmed by immunohistochemistry (IHC) staining in the lungs of a well-established sepsis mouse model. We found that all the four genes were upregulated in semiquantitative RT-PCR studies; however, MMP9 showed a nonsignificant increase in expression. MPO staining showed strong immunoreactivity in sepsis as compared to the control. This study demonstrates the role of significant and widespread immune activation (IL1R2, MMP9), along with oxidative stress (ARG1) and the recruitment of neutrophils, in sepsis (ELANE, MPO). Full article

(This article belongs to the Special Issue The Role of Genotoxicity in Infertility and Cancer Development)

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18 pages, 2017 KiB

Open AccessArticle

Genistein Modulates Signaling Pathways and Targets Several Epigenetic Markers in HeLa Cells

by Madhumitha Kedhari Sundaram, Sreepoorna Unni, Pallavi Somvanshi, Tulika Bhardwaj, Raju K. Mandal, Arif Hussain and Shafiul Haque

Genes 2019, 10(12), 955; https://0-doi-org.brum.beds.ac.uk/10.3390/genes10120955 - 21 Nov 2019

Cited by 28 | Viewed by 3748

Abstract

Background: Several epigenetic changes are responsible for transcriptional alterations of signaling pathways and tumour suppressor genes (TSGs) contributing to carcinogenesis. This study was aimed to examine the effect of the phytochemical, genistein on various molecular targets in HeLa cells. Methods: Quantitative PCR was used to analyze the expression of various molecular targets. Biochemical assays were employed to study the epigenetic enzymes. To correlate the transcriptional status of the selected TSGs and epigenetic modulation, their promoter 5’CpG methylation levels were evaluated by quantitative methylation array followed by methylation specific restriction digestion. Results: The expression of several genes involved in the cell cycle regulation, migration, inflammation, phosphatidylinositol 3-kinase (PI3K) and mitogen activated kinase-like protein (MAPK) pathway were found to be modulated including CCNB1, TWIST1, MMP14, TERT, AKT1, PTPRR, FOS and IL1A. Genistein modulated the expression of DNA methyltransferases (DNMTs), histone deacetylases (HDACs), histone methyltransferases (HMTs), demethylases, and histone phosphorylases. Furthermore, genistein decreased the activity of DNMTs, HDACs, and HMTs and reduced global DNA methylation levels. Promoter methylation of several TSGs, including FHIT, RUNX3, CDH1, PTEN, and SOC51, was lowered with corresponding transcriptional increase. Network analysis indicated similar effect of genistein. Conclusion: This study presents a comprehensive mechanism of action of genistein showcasing effective epigenetic modulation and widespread transcriptional changes resulting in restoration of tumour suppressor gene expression. This study corroborates the development of genistein as a candidate for anti-cancer therapy. Full article

(This article belongs to the Special Issue The Role of Genotoxicity in Infertility and Cancer Development)

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22 pages, 5893 KiB

Open AccessArticle

Investigation of Precise Molecular Mechanistic Action of Tobacco-Associated Carcinogen ‘NNK’ Induced Carcinogenesis: A System Biology Approach

by Anukriti, Anupam Dhasmana, Swati Uniyal, Pallavi Somvanshi, Uma Bhardwaj, Meenu Gupta, Shafiul Haque, Mohtashim Lohani, Dhruv Kumar, Janne Ruokolainen and Kavindra Kumar Kesari

Genes 2019, 10(8), 564; https://0-doi-org.brum.beds.ac.uk/10.3390/genes10080564 - 26 Jul 2019

Cited by 9 | Viewed by 3436

Abstract

Cancer is the second deadliest disease listed by the WHO. One of the major causes of cancer disease is tobacco and consumption possibly due to its main component, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). A plethora of studies have been conducted in the past aiming to decipher the association of NNK with other diseases. However, it is strongly linked with cancer development. Despite these studies, a clear molecular mechanism and the impact of NNK on various system-level networks is not known. In the present study, system biology tools were employed to understand the key regulatory mechanisms and the perturbations that will happen in the cellular processes due to NNK. To investigate the system level influence of the carcinogen, NNK rewired protein–protein interaction network (PPIN) was generated from 544 reported proteins drawn out from 1317 articles retrieved from PubMed. The noise was removed from PPIN by the method of modulation. Gene ontology (GO) enrichment was performed on the seed proteins extracted from various modules to find the most affected pathways by the genes/proteins. For the modulation, Molecular COmplex DEtection (MCODE) was used to generate 19 modules containing 115 seed proteins. Further, scrutiny of the targeted biomolecules was done by the graph theory and molecular docking. GO enrichment analysis revealed that mostly cell cycle regulatory proteins were affected by NNK. Full article

(This article belongs to the Special Issue The Role of Genotoxicity in Infertility and Cancer Development)

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13 pages, 5100 KiB

Open AccessArticle

Sperm Proteome Analysis and Identification of Fertility-Associated Biomarkers in Unexplained Male Infertility

by Manesh Kumar Panner Selvam, Ashok Agarwal, Peter Natesan Pushparaj, Saradha Baskaran and Hocine Bendou

Genes 2019, 10(7), 522; https://0-doi-org.brum.beds.ac.uk/10.3390/genes10070522 - 11 Jul 2019

Cited by 41 | Viewed by 5158

Abstract

Up to 30% of men with normal semen parameters suffer from infertility and the reason for this is unknown. Altered expression of sperm proteins may be a major cause of infertility in these men. Proteomic profiling was performed on pooled semen samples from eight normozoospermic fertile men and nine normozoospermic infertile men using LC-MS/MS. Furthermore, key differentially expressed proteins (DEPs) related to the fertilization process were selected for validation using Western blotting. A total of 1139 and 1095 proteins were identified in normozoospermic fertile and infertile men, respectively. Of these, 162 proteins were identified as DEPs. The canonical pathway related to free radical scavenging was enriched with upregulated DEPs in normozoospermic infertile men. The proteins associated with reproductive system development and function, and the ubiquitination pathway were underexpressed in normozoospermic infertile men. Western blot analysis revealed the overexpression of annexin A2 (ANXA2) (2.03 fold change; P = 0.0243), and underexpression of sperm surface protein Sp17 (SPA17) (0.37 fold change; P = 0.0205) and serine protease inhibitor (SERPINA5) (0.32 fold change; P = 0.0073) in men with unexplained male infertility (UMI). The global proteomic profile of normozoospermic infertile men is different from that of normozoospermic fertile men. Our data suggests that SPA17, ANXA2, and SERPINA5 may potentially serve as non-invasive protein biomarkers associated with the fertilization process of the spermatozoa in UMI. Full article

(This article belongs to the Special Issue The Role of Genotoxicity in Infertility and Cancer Development)

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Review

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14 pages, 1188 KiB

Open AccessReview

A “NOTCH” Deeper into the Epithelial-To-Mesenchymal Transition (EMT) Program in Breast Cancer

by Rohan Kar, Niraj Kumar Jha, Saurabh Kumar Jha, Ankur Sharma, Sunny Dholpuria, Nidhi Asthana, Kundan Chaurasiya, Vivek Kumar Singh, Shuaib Burgee and Parma Nand

Genes 2019, 10(12), 961; https://0-doi-org.brum.beds.ac.uk/10.3390/genes10120961 - 22 Nov 2019

Cited by 51 | Viewed by 5813

Abstract

Notch signaling is a primitive signaling pathway having various roles in the normal origin and development of each multicellular organisms. Therefore, any aberration in the pathway will inevitably lead to deadly outcomes such as cancer. It has now been more than two decades since Notch was acknowledged as an oncogene in mouse mammary tumor virus-infected mice. Since that discovery, activated Notch signaling and consequent up-regulation of tumor-promoting Notch target genes have been observed in human breast cancer. Moreover, consistent over-expression of Notch ligands and receptors has been shown to correlate with poor prognosis in human breast cancer. Notch regulates a number of key processes during breast carcinogenesis, of which, one key phenomenon is epithelial–mesenchymal transition (EMT). EMT is a key process for large-scale cell movement during morphogenesis at the time of embryonic development. Cancer cells aided by transcription factors usurp this developmental program to execute the multi-step process of tumorigenesis and metastasis. In this review, we recapitulate recent progress in breast cancer research that has provided new perceptions into the molecular mechanisms behind Notch-mediated EMT regulation during breast tumorigenesis. Full article

(This article belongs to the Special Issue The Role of Genotoxicity in Infertility and Cancer Development)

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22 pages, 1863 KiB

Open AccessReview

MicroRNA in Pancreatic Cancer: From Biology to Therapeutic Potential

by Manmeet Rawat, Kavita Kadian, Yash Gupta, Anand Kumar, Patrick S.G. Chain, Olga Kovbasnjuk, Suneel Kumar and Gulshan Parasher

Genes 2019, 10(10), 752; https://0-doi-org.brum.beds.ac.uk/10.3390/genes10100752 - 25 Sep 2019

Cited by 87 | Viewed by 7147

Abstract

Pancreatic cancer is one of the most aggressive malignancies, accounting for more than 45,750 deaths annually in the U.S. alone. The aggressive nature and late diagnosis of pancreatic cancer, coupled with the limitations of existing chemotherapy, present the pressing need for the development of novel therapeutic strategies. Recent reports have demonstrated a critical role of microRNAs (miRNAs) in the initiation, progression, and metastasis of cancer. Furthermore, aberrant expressions of miRNAs have often been associated with the cause and consequence of pancreatic cancer, emphasizing the possible use of miRNAs in the effective management of pancreatic cancer patients. In this review, we provide a brief overview of miRNA biogenesis and its role in fundamental cellular process and miRNA studies in pancreatic cancer patients and animal models. Subsequent sections narrate the role of miRNA in, (i) cell cycle and proliferation; (ii) apoptosis; (iii) invasions and metastasis; and (iv) various cellular signaling pathways. We also describe the role of miRNA’s in pancreatic cancer; (i) diagnosis; (ii) prognosis and (iii) therapeutic intervention. Conclusion section describes the gist of review with future directions. Full article

(This article belongs to the Special Issue The Role of Genotoxicity in Infertility and Cancer Development)

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