Evaluation of the target genes of arsenic trioxide in pancreatic cancer by bioinformatics analysis

Zhou, Chen; Gong, Liuyun; Long, Rong; Weng, Ningna; Feng, Yao‐Yue; Dong, Yanyan; Zhu, Hong; Zhao, Youwei; Zhang, Yuanyuan; Zhu, Qing; Han, Suxia

doi:10.3892/ol.2019.10889

Cited by 4 publications

(4 citation statements)

References 43 publications

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“…Arsenite showed the ability to induce S-phase arrest, autophagy and apoptosis on various tumors by modulating genes such as Forkhead box O3 (FOXO3a) and Cyclin D1 (CCND1) [74], or sustaining inhibition of mTORC1 [7], the latter of which was shown to be related to autophagy regulation. The mTOR pathway is activated through IL6 signaling, which is closely related to cell growth and metastasis in TNBC [53,54].…”

Section: Discussionmentioning

confidence: 99%

Targeting Cell Death Mechanism Specifically in Triple Negative Breast Cancer Cell Lines

Pruteanu

Braicu

Módos

et al. 2022

IJMS

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Triple negative breast cancer (TNBC) is currently associated with a lack of treatment options. Arsenic derivatives have shown antitumoral activity both in vitro and in vivo; however, their mode of action is not completely understood. In this work we evaluate the response to arsenate of the double positive MCF-7 breast cancer cell line as well as of two different TNBC cell lines, Hs578T and MDA-MB-231. Multimodal experiments were conducted to this end, using functional assays and microarrays. Arsenate was found to induce cytoskeletal alteration, autophagy and apoptosis in TNBC cells, and moderate effects in MCF-7 cells. Gene expression analysis showed that the TNBC cell lines’ response to arsenate was more prominent in the G2M checkpoint, autophagy and apoptosis compared to the Human Mammary Epithelial Cells (HMEC) and MCF-7 cell lines. We confirmed the downregulation of anti-apoptotic genes (MCL1, BCL2, TGFβ1 and CCND1) by qRT-PCR, and on the protein level, for TGFβ2, by ELISA. Insight into the mode of action of arsenate in TNBC cell lines it is provided, and we concluded that TNBC and non-TNBC cell lines reacted differently to arsenate treatment in this particular experimental setup. We suggest the future research of arsenate as a treatment strategy against TNBC.

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Section: Discussionmentioning

confidence: 99%

Targeting Cell Death Mechanism Specifically in Triple Negative Breast Cancer Cell Lines

Pruteanu

Braicu

Módos

et al. 2022

IJMS

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“…Studies employing other approaches have also searched for target genes associated with arsenic compounds using various cancers; for example, total arsenic concentration was related to the risk of upper tract urothelial carcinoma (UTUC), and the independent polymorphisms of the AS3MT gene were related to the risk of UTUC and bladder cancer [ 59 ]. Another study reported 19 ATO target genes associated with multiple cancer types (the most common association being pancreatic cancer) [ 60 ]. Six of these genes (AKT1, CCND1, CDKN2A, IKBKB, MAPK1, and MAPK3) were strongly associated and were used to find further mutation information.…”

Section: Discussionmentioning

confidence: 99%

Association between Arsenic Level, Gene Expression in Asian Population, and In Vitro Carcinogenic Bladder Tumor

Singhal

Ruprecht

Sens

et al. 2022

Oxidative Medicine and Cellular Longevity

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The IARC classified arsenic (As) as “carcinogenic to humans.” Despite the health consequences of arsenic exposure, there is no molecular signature available yet that can predict when exposure may lead to the development of disease. To understand the molecular processes underlying arsenic exposure and the risk of disease development, this study investigated the functional relationship between high arsenic exposure and disease risk using gene expression derived from human exposure. In this study, a three step analysis was employed: (1) the gene expression profiles obtained from two diverse arsenic-exposed Asian populations were utilized to identify differentially expressed genes associated with arsenic exposure in human subjects, (2) the gene expression profiles induced by arsenic exposure in four different myeloma cancer cell lines were used to define common genes and pathways altered by arsenic exposure, and (3) the genetic profiles of two publicly available human bladder cancer studies were used to test the significance of the common association of genes, identified in step 1 and step 2, to develop and validate a predictive model of primary bladder cancer risk associated with arsenic exposure. Our analysis shows that arsenic exposure to humans is mainly associated with organismal injury and abnormalities, immunological disease, inflammatory disease, gastrointestinal disease, and increased rates of a wide variety of cancers. In addition, arsenic exerts its toxicity by generating reactive oxygen species (ROS) and increasing ROS production causing the imbalance that leads to cell and tissue damage (oxidative stress). Oxidative stress activates inflammatory pathways leading to transformation of a normal cell to tumor cell specifically; there is significant evidence of the advancing changes in oxidative/nitrative stress during the progression of bladder cancer. Therefore, we examined the relation of differentially expressed genes due to exposure of arsenic in human and bladder cancer and developed a bladder cancer risk prediction model. In this study, integrin-linked kinase (ILK) was one of the most significant pathways identified between both arsenic exposed population which plays a key role in eliciting a protective response to oxidative damage in epidermal cells. On the other hand, several studies showed that arsenic trioxide (ATO) is useful for anticancer therapy although the mechanisms underlying its paradoxical effects are still not well understood. ATO has shown remarkable efficacy for the treatment of multiple myeloma; therefore, it will be helpful to understand the underlying cancer biology by which ATO exerts its inhibitory effect on the myeloma cells. Our study found that MAPK is one of the most active network between arsenic gene and ATO cell line which is involved in indicative of oxidative/nitrosative damage and well associated with the development of bladder cancer. The study identified a unique set of 147 genes associated with arsenic exposure and linked to molecular mechanisms of cancer. The risk prediction model shows the highest prediction ability for recurrent bladder tumors based on a very small subset (NKIRAS2, AKTIP, and HLA-DQA1) of the 147 genes resulting in AUC of 0.94 (95% CI: 0.744-0.995) and 0.75 (95% CI: 0.343-0.933) on training and validation data, respectively.

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“…Activating mutations of KRAS and NRAS are common in de novo AML, occurring in 11-16% and 4-5%, respectively, and associated with decreased survival (Ball et al, 2019). Previous studies in solid tumors have shown that knockdown of NEAT1 leads to suppression of cancer progression, via suppression of oncogenic pathways that encompassed the RAS proteins (Gong et al, 2016;Zhou et al, 2019). The upregulated NEAT1 expression in mutant ASXL1, KRAS, and NRAS AML patients, supports the notion that control of NEAT1 expression could be orchestrated, and depend upon several different factors.…”

Section: Discussionmentioning

confidence: 99%

The biological and prognostic role of long non-coding RNA NEAT1 in acute myeloid leukemia

Miliara

Neddermeyer

Bonetti

et al. 2022

Preprint

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Nuclear paraspeckle assembly transcript 1 (NEAT1) is a long non-coding RNA associated with the promotion of several solid cancers. As part of the FANTOM6 project, we aimed to define its role in acute myeloid leukemia (AML) and myelopoiesis, since it remains largely uninvestigated. We show that NEAT1 expression increases during myelopoiesis, especially in monocytes. NEAT1 expression is elevated in AML compared to normal bone marrow (NBM), especially in AML with inv(16)and t(8;21). In addition, NEAT1 expression correlates positively with ASXL1, KRAS and NRAS mutations, but negatively with TP53 mutant AML. Higher NEAT1 expression is associated with better overall survival in AML, independent of other known risk factors. Knockdown of NEAT1 in AML cells induces monocytic differentiation and upregulated gene expression of genes involved in glucose metabolism. By investigating genome-wide RNA and DNA interactions using RADICL-sequencing, we show that NEAT1 binds to the RUNX2 locus that is associated with differentiation, metabolism, and glucose uptake. The results suggest that the lncRNA NEAT1 has a role in myelopoiesis, AML and is implicated in glycolysis.

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Evaluation of the target genes of arsenic trioxide in pancreatic cancer by bioinformatics analysis

Cited by 4 publications

References 43 publications

Targeting Cell Death Mechanism Specifically in Triple Negative Breast Cancer Cell Lines

Targeting Cell Death Mechanism Specifically in Triple Negative Breast Cancer Cell Lines

Association between Arsenic Level, Gene Expression in Asian Population, and In Vitro Carcinogenic Bladder Tumor

The biological and prognostic role of long non-coding RNA NEAT1 in acute myeloid leukemia

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