Study of APOBEC3B focused breast cancer pathways and the clinical relevance

Abstract APOBEC3B is considered as an enzymatic source of mutation in case of breast cancer and Human T-Cell Leukemia Virus Type 1 and Bone Leiomyosarcoma are also associated with it. The major functions controlled or affected due to APOBEC3B are gene expression, mRNA editing such as C -> U conversion, and deoxycytidine deaminase activity. Here, the main goal of the study was to perform a systematic analysis of APOBEC3B associated genes and its functional impact in human breast cancer. For this purpose, the datasets have been utilized from the publicly available database such as GEO, OncoLnc, and TCGA. Based on the requirements for fetching the values, different bioinformatics approaches have been applied at different levels. Further, co-regulated genes obtained from co-expression network have been processed and the mutated genes with the pathways enrichment analysis, and the clinical relevance using survival curve analysis by using OncoLnc have been performed. In the results, we found that there are a number of critical pathways known to directly associated with breast cancer are altered because of the genes which are either overexpressed or top mutated and are associated with APOBEC3B and these pathways are cell cycle, p53 signaling, immune signaling pathways, progesterone-mediated oocyte maturation, apoptosis, critical metabolic pathways, and pathways in cancers. From the mutational and survival analysis data, we also observe that there are a number of well-known cancer associated signaling pathways (mainly cancer), immune signaling pathway, critical metabolic associated pathways, cell cycle, ubiquitin-proteasomal signaling pathways, and p53 signaling. Network-level study of pathways and their components CD40LG as the potential gene where CD40LG is directly affecting 10 pathways and most of them are the parts of immune system and known to control a number of leading human diseases including cancers.

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Targeted Delivery of Natural Bioactives and Lipid-nanocargos against Signaling Pathways Involved in Skin Cancer

Current Medicinal Chemistry ◽

10.2174/0929867327666201104151752 ◽

2020 ◽

Vol 27 ◽

Author(s):

Mohammad Kashif Iqubal ◽

Aiswarya Chaudhuri ◽

Ashif Iqubal ◽

Sadaf Saleem ◽

Madan Mohan Gupta ◽

...

Keyword(s):

Skin Cancer ◽

Signaling Pathways ◽

Signaling Pathway ◽

Targeted Delivery ◽

Skin Pigmentation ◽

Wnt Signaling Pathway ◽

Human Beings ◽

Radiation Chemical ◽

Cell Leukemia Virus Type ◽

Human T Cell

: At present, skin cancer is a widespread malignancy in human beings. Among diverse population types, Caucasian populations are much more prone in comparison to darker skin populations due to the comparative lack of skin pigmentation. Skin cancer is divided into malignant and non-melanoma skin cancer, which is additionally categorized as basal and squamous cell carcinoma. The exposure to ultraviolet radiation, chemical carcinogen (polycyclic aromatic hydrocarbons, arsenic, tar, etc.), and viruses (herpes virus, human papillomavirus, and human T-cell leukemia virus type-1) are major contributing factors of skin cancer. There are distinct pathways available through which skin cancer develops, such as the JAKSTAT pathway, Akt pathway, MAPKs signaling pathway, Wnt signaling pathway, to name a few. Currently, several targeted treatments are available, such as monoclonal antibodies, which have dramatically changed the line of treatment of this disease but possess major therapeutic limitations. Thus, recently many phytochemicals have been evaluated either alone or in combination with the existing synthetic drugs to overcome their limitations and have found to play a promising role in the prevention and treatment. In this review, complete tracery of skin cancer, starting from the signaling pathways involved, newer developed drugs with their targets and limitations along with the emerging role of natural products alone or in combination as potent anticancer agents and their molecular mechanism involved has been discussed. Apart from this, various nanocargos have also been mentioned here, which can play a significant role in the management and treatment of different types of skin cancer.

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5,6,7,3′,4′,5′-Hexamethoxyflavone inhibits growth of triple-negative breast cancer cells via suppression of MAPK and Akt signaling pathways and arresting cell cycle

International Journal of Oncology ◽

10.3892/ijo.2017.4157 ◽

2017 ◽

Vol 51 (6) ◽

pp. 1685-1693 ◽

Cited By ~ 7

Author(s):

Natasha Borah ◽

Shimara Gunawardana ◽

Haydee Torres ◽

Susan McDonnell ◽

Severine Van Slambrouck

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Cancer Cells ◽

Signaling Pathways ◽

Triple Negative Breast Cancer ◽

Breast Cancer Cells ◽

Triple Negative ◽

Akt Signaling

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Human T-Cell Leukemia Virus Type 1 Infection Leads to Arrest in the G1 Phase of the Cell Cycle

Journal of Virology ◽

10.1128/jvi.00091-08 ◽

2008 ◽

Vol 82 (17) ◽

pp. 8442-8455 ◽

Cited By ~ 35

Author(s):

Meihong Liu ◽

Liangpeng Yang ◽

Ling Zhang ◽

Baoying Liu ◽

Randall Merling ◽

...

Keyword(s):

Cell Cycle ◽

T Cells ◽

T Cell ◽

Leukemia Virus ◽

T Cell Leukemia ◽

Cell Leukemia ◽

Cell Leukemia Virus Type ◽

Human T Cell ◽

T Cell Leukemia Virus

ABSTRACT Infection by the human T-cell leukemia virus type 1 (HTLV-1) is thought to cause dysregulated T-cell proliferation, which in turn leads to adult T-cell leukemia/lymphoma. Early cellular changes after HTLV-1 infection have been difficult to study due to the poorly infectious nature of HTLV-1 and the need for cell-to-cell contact for HTLV-1 transmission. Using a series of reporter systems, we show that HeLa cells cease proliferation within one or two division cycles after infection by HTLV-1 or transduction of the HTLV-1 tax gene. HTLV-1-infected HeLa cells, like their tax-transduced counterparts, expressed high levels of p21 CIP1/WAF1 and p27 KIP1 , developed mitotic abnormalities, and became arrested in G1 in senescence. In contrast, cells of a human osteosarcoma lineage (HOS) continued to divide after HTLV-1 infection or Tax expression, albeit at a reduced growth rate and with mitotic aberrations. Unique to HOS cells is the dramatic reduction of p21 CIP1/WAF1 and p27 KIP1 expression, which is in part associated with the constitutive activation of the phosphatidylinositol-3-kinase (PI3K)-protein kinase B (Akt) pathway. The loss of p21 CIP1/WAF1 and p27 KIP1 in HOS cells apparently allows HTLV-1- and Tax-induced G1 arrest to be bypassed. Finally, HTLV-1 infection and Tax expression also cause human SupT1 T cells to arrest in the G1 phase of the cell cycle. These results suggest that productive HTLV-1 infection ordinarily leads to Tax-mediated G1 arrest. However, T cells containing somatic mutations that inactivate p21 CIP1/WAF1 and p27 KIP1 may continue to proliferate after HTLV-1 infection and Tax expression. These infected cells can expand clonally, accumulate additional chromosomal abnormalities, and progress to cancer.

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Oridonin induces G2/M cell cycle arrest and apoptosis through MAPK and p53 signaling pathways in HepG2 cells

Oncology Reports ◽

10.3892/or_00000903 ◽

2010 ◽

Vol 24 (3) ◽

Cited By ~ 1

Author(s):

Keyword(s):

Cell Cycle ◽

Cell Cycle Arrest ◽

Signaling Pathways ◽

Hepg2 Cells ◽

M Cell ◽

P53 Signaling ◽

Cycle Arrest

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Human T-cell leukemia virus type 1 Tax releases cell cycle arrest induced by p16INK4a.

Journal of Virology ◽

10.1128/jvi.71.3.1956-1962.1997 ◽

1997 ◽

Vol 71 (3) ◽

pp. 1956-1962 ◽

Cited By ~ 92

Author(s):

K G Low ◽

L F Dorner ◽

D B Fernando ◽

J Grossman ◽

K T Jeang ◽

...

Keyword(s):

Cell Cycle ◽

T Cell ◽

Cell Cycle Arrest ◽

Leukemia Virus ◽

Cell Leukemia ◽

Cell Leukemia Virus Type ◽

Cycle Arrest ◽

Human T Cell ◽

T Cell Leukemia Virus

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Twist promotes reprogramming of glucose metabolism in breast cancer cells through PI3K/AKT and p53 signaling pathways

Oncotarget ◽

10.18632/oncotarget.4697 ◽

2015 ◽

Vol 6 (28) ◽

pp. 25755-25769 ◽

Cited By ~ 50

Author(s):

Li Yang ◽

Yixuan Hou ◽

Jie Yuan ◽

Shifu Tang ◽

Hailong Zhang ◽

...

Keyword(s):

Breast Cancer ◽

Glucose Metabolism ◽

Cancer Cells ◽

Signaling Pathways ◽

Breast Cancer Cells ◽

P53 Signaling

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Whole transcriptome sequencing in metastatic cancer: A review of expression outliers in 113 metastatic breast cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.3080 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 3080-3080

Author(s):

Nathalie LeVasseur ◽

Veronika Csizmok ◽

Melika Bonakdar ◽

Yaoqing Shen ◽

Lindsay Zibrik ◽

...

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Clinical Relevance ◽

Transcriptome Sequencing ◽

Metastatic Breast ◽

High Expression ◽

Histological Subtypes ◽

Whole Transcriptome Sequencing ◽

Whole Transcriptome ◽

Low Expression

3080 Background: The genomic profiling of breast cancers has led to a greater understanding of the mutational landscape of metastatic breast cancer (MBC) with potential therapeutic implications. Despite these advances, there is a paucity of data regarding the additive value and relevance of gene expression across histological and molecular subtypes, which represents the majority of informative and actionable findings identified in the BC Cancer personalized oncogenomics program (POG). Methods: Informative findings with potential clinical application from whole genome sequencing (WGS) and whole transcriptome sequencing (WTS) in MBC patients between 2012-2018 were reviewed. Variants observed in pathway genes of potential clinical relevance, as defined by a curated list of genes, were examined across histological subtypes. High and low expression outliers relative to TCGA breast cases, defined as expression greater than 98th percentile and FC > 2 compared to Illumina breast dataset and lower than 25th percentile and FC < -2 compared to Illumina breast dataset, respectively, were then analyzed to establish how many outliers were observed in pathways of potential clinical relevance. Results: A total of 113 cases were included. WGS revealed that TP53 was the most frequent single nucleotide variant (SNV) in triple negative breast cancer (23/30, 77%), whereas PIK3CA (37/78, 47%), PTEN (11/78, 14%) and ESR1 (19/78, 24%) were most frequent in ER positive cases and CDKN2A (2/18, 11%) in HER2 positive cases. Across all subtypes, the mTOR and cell cycle pathways were found to have the highest frequency of SNVs, with the identification of 86 and 71 variants, respectively. Expression data for 113 RNA-sequenced patients revealed a high frequency of expression outliers in the mTOR pathway (26 high expression and 424 low expression outlier genes) and cell cycle pathways (35 high expression and 331 low expression outlier genes), but also in the WNT pathway (96 high expression and 490 lower expression outlier genes) and NOTCH pathway (84 high expression and 564 low expression outlier genes). Conclusions: Frequently identified SNVs across histological subtypes were correlated with expression outliers in pathways of clinical relevance in breast cancer. Additional informative findings, in pathways of potential clinical relevance not historically targeted in breast cancer, were identified with WTS. The clinical utility of these findings warrants further study.

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