Interplay Between Mitochondrial Peroxiredoxins and ROS in Cancer Development and Progression

Mitochondria are multifunctional cellular organelles that are major producers of reactive oxygen species (ROS) in eukaryotes; to maintain the redox balance, they are supplemented with different ROS scavengers, including mitochondrial peroxiredoxins (Prdxs). Mitochondrial Prdxs have physiological and pathological significance and are associated with the initiation and progression of various cancer types. In this review, we have focused on signaling involving ROS and mitochondrial Prdxs that is associated with cancer development and progression. An upregulated expression of Prdx3 and Prdx5 has been reported in different cancer types, such as breast, ovarian, endometrial, and lung cancers, as well as in Hodgkin’s lymphoma and hepatocellular carcinoma. The expression of Prdx3 and Prdx5 in different types of malignancies involves their association with different factors, such as transcription factors, micro RNAs, tumor suppressors, response elements, and oncogenic genes. The microenvironment of mitochondrial Prdxs plays an important role in cancer development, as cancerous cells are equipped with a high level of antioxidants to overcome excessive ROS production. However, an increased production of Prdx3 and Prdx5 is associated with the development of chemoresistance in certain types of cancers and it leads to further complications in cancer treatment. Understanding the interplay between mitochondrial Prdxs and ROS in carcinogenesis can be useful in the development of anticancer drugs with better proficiency and decreased resistance. However, more targeted studies are required for exploring the tumor microenvironment in association with mitochondrial Prdxs to improve the existing cancer therapies and drug development.

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COPB2: a transport protein with multifaceted roles in cancer development and progression

Clinical & Translational Oncology ◽

10.1007/s12094-021-02630-9 ◽

2021 ◽

Author(s):

Y. Feng ◽

X. Lei ◽

L. Zhang ◽

H. Wan ◽

H. Pan ◽

...

Keyword(s):

Cell Proliferation ◽

Protein Complex ◽

Current Knowledge ◽

Cancer Development ◽

Tumor Cell Proliferation ◽

Invasion And Metastasis ◽

Hallmarks Of Cancer ◽

Cancer Types ◽

Beta 2 ◽

Cellular Organelles

AbstractThe Coatomer protein complex subunit beta 2 (COPB2) is involved in the formation of the COPI coatomer protein complex and is responsible for the transport of vesicles between the Golgi apparatus and the endoplasmic reticulum. It plays an important role in maintaining the integrity of these cellular organelles, as well as in maintaining cell homeostasis. More importantly, COPB2 plays key roles in embryonic development and tumor progression. COPB2 is regarded as a vital oncogene in several cancer types and has been implicated in tumor cell proliferation, survival, invasion, and metastasis. Here, we summarize the current knowledge on the roles of COPB2 in cancer development and progression in the context of the hallmarks of cancer.

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Identification of BAP1-associated MicroRNAs and Implications in Cancer Development

10.31487/j.ijcst.2019.01.01 ◽

2019 ◽

pp. 1-4

Author(s):

Tikam Chand ◽

Tikam Chand

Keyword(s):

Gene Regulation ◽

In Silico ◽

Mirna Target ◽

Target Prediction ◽

Differential Regulation ◽

Cancer Development ◽

Mirna Target Prediction ◽

Cancer Types ◽

In Silico Tools

Having role in gene regulation and silencing, miRNAs have been implicated in development and progression of a number of diseases, including cancer. Herein, I present potential miRNAs associated with BAP1 gene identified using in-silico tools such as TargetScan and Exiqon miRNA Target Prediction. I identified fifteen highly conserved miRNA (hsa-miR-423-5p, hsa-miR-3184-5p, hsa-miR-4319, hsa-miR125b-5p, hsa-miR-125a-5p, hsa-miR-6893-3p, hsa-miR-200b-3p, hsa-miR-200c-3p, hsa-miR-505-3p.1, hsa-miR-429, hsa-miR-370-3p, hsa-miR-125a-5p, hsa-miR-141-3p, hsa-miR-200a-3p, and hsa-miR-429) associated with BAP1 gene. We also predicted the differential regulation of these twelve miRNAs in different cancer types.

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Anticancer Immunotoxins, Challenges, and Approaches

Current Pharmaceutical Design ◽

10.2174/1381612826666201006155346 ◽

2020 ◽

Vol 26 ◽

Author(s):

Maryam Dashtiahangar ◽

Leila Rahbarnia ◽

Safar Farajnia ◽

Arash Salmaninejad ◽

Arezoo Gowhari Shabgah ◽

...

Keyword(s):

Therapeutic Strategy ◽

Antibody Fragment ◽

Clinical Use ◽

Multiple Cancer ◽

Main Obstacle ◽

Cancer Types ◽

Recombinant Immunotoxins ◽

Cancerous Cells ◽

High Immunogenicity ◽

Novel Therapeutic

: The development of recombinant immunotoxins (RITs) as a novel therapeutic strategy has made a revolution in the treatment of cancer. RITs are resulting from the fusion of antibodies to toxin proteins for targeting and eliminating cancerous cells by inhibiting protein synthesis. Despite indisputable outcomes of RITs regarding inhibiting multiple cancer types, high immunogenicity has been known as the main obstacle in the clinical use of RITs. Various strategies have been proposed to overcome these limitations, including immunosuppressive therapy, humanization of the antibody fragment moiety, generation of immunotoxins originated from endogenous human cytotoxic enzymes, and modification of the toxin moiety to escape the immune system. This paper devoted to reviewing recent advances in the design of immunotoxins with lower immunogenicity.

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Breast Cancer Resistance Protein: A Potential Therapeutic Target for Cancer

Current Drug Targets ◽

10.2174/1389450121999201125200132 ◽

2020 ◽

Vol 21 ◽

Author(s):

Sonali Mehendale-Munj

Keyword(s):

Breast Cancer ◽

Breast Cancer Resistance Protein ◽

Protein A ◽

The Body ◽

Cancer Therapies ◽

Cancer Resistance ◽

Lung Cancers ◽

Resistance Protein ◽

Atp Regulation ◽

Treatment Procedures

: Breast Cancer Resistance Protein (BCRP) is an efflux transporter responsible for causing multidrug re-sistance(MDR). It is known to expel many potent antineoplastic drugs, owing to its efflux function. Efflux of chemothera-peutics because of BCRP develops resistance to manydrugs, leading to failure in cancer treatment. BCRP plays an important role in physiology by protecting the organism from xenobiotics and other toxins. It is a half-transporter affiliated to theATP-binding cassette (ABC) superfamily of transporters, encoded by the gene ABCG2 and functions in response to adenosine triphosphate (ATP). Regulation of BCRP expression is critically controlled at molecular levels which help in maintaining the balance of xenobiotics and nutrients inside the body. Expression of BCRP can be found in brain, liver, lung cancers and acute myeloid leukemia (AML). Moreover, it is also expressed at high levels in stem cells and many cell lines. This frequent expression of BCRP has an impact on the treatment procedures and if not scrutinized may lead to failure of many cancer therapies.

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Recent Advancements on Immunomodulatory Mechanisms of Resveratrol in Tumor Microenvironment

Molecules ◽

10.3390/molecules26051343 ◽

2021 ◽

Vol 26 (5) ◽

pp. 1343

Author(s):

Gagan Chhabra ◽

Chandra K. Singh ◽

Deeba Amiri ◽

Neha Akula ◽

Nihal Ahmad

Keyword(s):

Tumor Microenvironment ◽

Immune Cell ◽

Cancer Therapies ◽

Regulatory Cells ◽

Immunomodulatory Effects ◽

Cancer Management ◽

Natural Agents ◽

Anticancer Effects ◽

Cancer Types ◽

Immune Related Genes

Immunomodulation of the tumor microenvironment is emerging as an important area of research for the treatment of cancer patients. Several synthetic and natural agents are being investigated for their ability to enhance the immunogenic responses of immune cells present in the tumor microenvironment to impede tumor cell growth and dissemination. Among them, resveratrol, a stilbenoid found in red grapes and many other natural sources, has been studied extensively. Importantly, resveratrol has been shown to possess activity against various human diseases, including cancer. Mechanistically, resveratrol has been shown to regulate an array of signaling pathways and processes involving oxidative stress, inflammation, apoptosis, and several anticancer effects. Furthermore, recent research suggests that resveratrol can regulate various cellular signaling events including immune cell regulation, cytokines/chemokines secretion, and the expression of several other immune-related genes. In this review, we have summarized recent findings on resveratrol’s effects on immune regulatory cells and associated signaling in various cancer types. Numerous immunomodulatory effects of resveratrol suggest it may be useful in combination with other cancer therapies including immunotherapy for effective cancer management.

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Landscape of Chimeric RNAs in Non-Cancerous Cells

Genes ◽

10.3390/genes12040466 ◽

2021 ◽

Vol 12 (4) ◽

pp. 466

Author(s):

Chen Chen ◽

Samuel Haddox ◽

Yue Tang ◽

Fujun Qin ◽

Hui Li

Keyword(s):

Cancer Cells ◽

Cell Lines ◽

Drug Targets ◽

Neoplastic Cell ◽

Multiple Cancer ◽

Chimeric Rnas ◽

Healthy Donors ◽

Cancer Types ◽

Chimeric Rna ◽

Cancerous Cells

Gene fusions and their products (RNA and protein) have been traditionally recognized as unique features of cancer cells and are used as ideal biomarkers and drug targets for multiple cancer types. However, recent studies have demonstrated that chimeric RNAs generated by intergenic alternative splicing can also be found in normal cells and tissues. In this study, we aim to identify chimeric RNAs in different non-neoplastic cell lines and investigate the landscape and expression of these novel candidate chimeric RNAs. To do so, we used HEK-293T, HUVEC, and LO2 cell lines as models, performed paired-end RNA sequencing, and conducted analyses for chimeric RNA profiles. Several filtering criteria were applied, and the landscape of chimeric RNAs was characterized at multiple levels and from various angles. Further, we experimentally validated 17 chimeric RNAs from different classifications. Finally, we examined a number of validated chimeric RNAs in different cancer and non-cancer cells, including blood from healthy donors, and demonstrated their ubiquitous expression pattern.

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MiRNA-200C expression in Fanconi anemia pathway functionally deficient lung cancers

Scientific Reports ◽

10.1038/s41598-021-83884-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Wenrui Duan ◽

Shirley Tang ◽

Li Gao ◽

Kathleen Dotts ◽

Andrew Fink ◽

...

Keyword(s):

Fanconi Anemia ◽

Epithelial Mesenchymal Transition ◽

Micro Rna ◽

Negative Regulator ◽

Migration And Invasion ◽

Pcr Analysis ◽

Tissue Samples ◽

Lung Cancers ◽

Mesenchymal Transition ◽

Micro Rnas

AbstractThe Fanconi Anemia (FA) pathway is essential for human cells to maintain genomic integrity following DNA damage. This pathway is involved in repairing damaged DNA through homologous recombination. Cancers with a defective FA pathway are expected to be more sensitive to cross-link based therapy or PARP inhibitors. To evaluate downstream effectors of the FA pathway, we studied the expression of 734 different micro RNAs (miRNA) using NanoString nCounter miRNA array in two FA defective lung cancer cells and matched control cells, along with two lung tumors and matched non-tumor tissue samples that were deficient in the FA pathway. Selected miRNA expression was validated with real-time PCR analysis. Among 734 different miRNAs, a cluster of microRNAs were found to be up-regulated including an important cancer related micro RNA, miR-200C. MiRNA-200C has been reported as a negative regulator of epithelial-mesenchymal transition (EMT) and inhibits cell migration and invasion by promoting the upregulation of E-cadherin through targeting ZEB1 and ZEB2 transcription factors. miRNA-200C was increased in the FA defective lung cancers as compared to controls. AmpliSeq analysis showed significant reduction in ZEB1 and ZEB2 mRNA expression. Our findings indicate the miRNA-200C potentially play a very important role in FA pathway downstream regulation.

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Taranto’s long shadow? Cancer mortality shows alarming peaks for specific types in the most polluted city of Italy but also in surrounding towns

10.1101/2020.12.18.20248464 ◽

2020 ◽

Author(s):

R. Roberto Cazzolla Gatti ◽

Alena Velichevskaya

Keyword(s):

Mortality Rate ◽

Industrial Area ◽

National Scale ◽

Policy Makers ◽

Specific Cancer ◽

Cancer Types ◽

Heavy Pollution ◽

High Level ◽

Epidemiological Effects ◽

The City

AbstractA national-scale study in Italy showed an incidence of cancer higher in the territories indicated as highly polluted compared to the regional average. One of them, the city of Taranto in Apulia (Italy), which is considered one of the most polluted cities in Europe, has numerous industrial activities that impact population health. We studied the epidemiological effects of a high level of pollution produced by the industrial area of Taranto in increasing the mortality rate for some specific cancer types in the city and towns of the two provinces located downwind. We analysed 10-year mortality rates for 14 major types of tumours reported among the residents of Taranto, of 6 surrounding towns, randomly placed within an imaginary cone in the main wind direction from the vertex of the industrial zone of Taranto. Our results confirm our hypothesis that the mortality rate for some specific types of cancer (namely, Hodgkin and non-Hodgkin lymphomas, leukaemia, liver and bladder tumours) are higher than the norm in the municipality of Taranto and we have evidence that other local causes may be implicated in the excess of mortality besides the potential dispersal of pollutants from the industrial area of Taranto. The proximity to the industrial area of Taranto cannot, therefore, explain alone the anomalies detected in some populations. It is likely that other site-specific sources of heavy pollution are playing a role in worsening the death toll of these towns and this must be taken into serious consideration by environmental policy-makers and local authorities.

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Automated Classification of Lung Cancer Types from Cytological Images Using Deep Convolutional Neural Networks

BioMed Research International ◽

10.1155/2017/4067832 ◽

2017 ◽

Vol 2017 ◽

pp. 1-6 ◽

Cited By ~ 44

Author(s):

Atsushi Teramoto ◽

Tetsuya Tsukamoto ◽

Yuka Kiriyama ◽

Hiroshi Fujita

Keyword(s):

Lung Cancer ◽

Cell Carcinoma ◽

Graphics Processing Unit ◽

Processing Unit ◽

Automated Classification ◽

Deep Convolutional Neural Networks ◽

Lung Cancers ◽

Microscopic Images ◽

Cancer Types

Lung cancer is a leading cause of death worldwide. Currently, in differential diagnosis of lung cancer, accurate classification of cancer types (adenocarcinoma, squamous cell carcinoma, and small cell carcinoma) is required. However, improving the accuracy and stability of diagnosis is challenging. In this study, we developed an automated classification scheme for lung cancers presented in microscopic images using a deep convolutional neural network (DCNN), which is a major deep learning technique. The DCNN used for classification consists of three convolutional layers, three pooling layers, and two fully connected layers. In evaluation experiments conducted, the DCNN was trained using our original database with a graphics processing unit. Microscopic images were first cropped and resampled to obtain images with resolution of 256 × 256 pixels and, to prevent overfitting, collected images were augmented via rotation, flipping, and filtering. The probabilities of three types of cancers were estimated using the developed scheme and its classification accuracy was evaluated using threefold cross validation. In the results obtained, approximately 71% of the images were classified correctly, which is on par with the accuracy of cytotechnologists and pathologists. Thus, the developed scheme is useful for classification of lung cancers from microscopic images.

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PAHs accumulation in soil-plant system in Atamanskoe lake bottom sediments in the long-term chemical contamination effect

10.5194/egusphere-egu21-12739 ◽

2021 ◽

Author(s):

Andrey Barbashev ◽

Abdulmalik Batukaev ◽

Svetlana Sushkova ◽

Tatiana Minkina ◽

Sarieh Tarigholizadeh ◽

...

Keyword(s):

Ultrastructural Changes ◽

Monitoring Site ◽

Chemical Contamination ◽

Russian Science ◽

Electron Microscopic ◽

Lake Bottom ◽

Polycyclic Aromatic ◽

Lake Bottom Sediments ◽

High Level ◽

Cellular Organelles

The concentrations of 16 priority polycyclic aromatic hydrocarbons (PAHs) in soils, under- and above-ground tissues of reed (Phragmites australis) on monitoring plots in the zone of industrial sewage tanks and sludge reservoirs in the city of Kamensk-Shakhtinskyi (southern Russia, Rostov Region), were determined. The total PAHs concentration in soil of monitoring site D3 (4229.4 &#177; 5.7&#181;g kg-1) was significantly higher than those in monitoring sites: D4 (3873.7 &#177; 17.1 &#181;g kg-1), TR1 (2217.3 &#177; 9.1&#181;g kg-1), 43 (2001.1 &#177; 13.0&#181;g kg-1), and also D0 (140.4 &#177; 1.0&#181;g kg-1) plots. Accordingly, the maximum accumulation was found for phenanthrene among the 16 priority PAHs in the most of the soil and plants samples. It was determined the PAHs pollution effect in the studied monitoring sites on cellular and sub-cellular organelles changes of P. australis. The data received shows that increasing of PAHs contamination negatively affected on the cellular and sub-cellular organelles changes of the studied pants. Using of electron-microscopic method for plants sub-cellular structure showed ultrastructural changes in the cell membranes, and the main cytoplasmic organelles of plant cells. It was established the P. australis had a high level of adaptation to the effect of stressors by using of tissue and cell levels. In general, the detected sub-cellular alterations under the PAHs effect were possibly connected to changes in biochemical and histochemical parameters as a response for reactive oxygen species and also as a protective response against oxidative stress. The results received carry in innovative findings for cellular and sub-cellular changes in plants exposed to 16 priority PAHs as very persistent and toxic contaminants.The research was financially supported by the Russian Science Foundation project no. 19-74-10046.

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