Genome organization in proximity to the <i>BAP1</i> locus appears to play a pivotal role in a variety of cancers

Sharma, Amit; Liu, Hongde; Tobar-Tosse, Fabián; Noll, Angela; Dakal, Tikam Chand; Li, Huamei; Holz, Frank G.; Loeffler, Karin U.; Herwig‐Carl, Martina C.

doi:10.1111/cas.14319

Cited by 11 publications

(5 citation statements)

References 38 publications

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“…The study revealed a high occurrence of DNA methylation‐mediated changes in FHL1 gene in mouth cancer, highlighting its significant relevance in the context of epigenetics 92 . Furthermore, previous studies have indicated that the involvement of loci‐specific (specifically on the X chromosome) and global long interspersed nuclear element‐1 (LINE‐1) repetitive sequence is associated with many forms of cancer 93–95 …”

Section: Tsgs X‐linked Tsgs and Their Involvement In Cancersmentioning

confidence: 85%

“…92 Furthermore, previous studies have indicated that the involvement of loci-specific (specifically on the X chromosome) and global long interspersed nuclear element-1 (LINE-1) repetitive sequence is associated with many forms of cancer. [93][94][95] Genes associated with cancer experience significant evolutionary selection. Researchers have proposed that Xlinked TSGs are not shielded by the Knudson's two-hit mechanism and are consequently susceptible to negative selection.…”

Section: And Evolutionary Aspectsmentioning

confidence: 99%

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Oncogenes and tumor suppressor genes: functions and roles in cancers

Dakal,

Dhabhai,

Pant

et al. 2024

MedComm

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Cancer, being the most formidable ailment, has had a profound impact on the human health. The disease is primarily associated with genetic mutations that impact oncogenes and tumor suppressor genes (TSGs). Recently, growing evidence have shown that X‐linked TSGs have specific role in cancer progression and metastasis as well. Interestingly, our genome harbors around substantial portion of genes that function as tumor suppressors, and the X chromosome alone harbors a considerable number of TSGs. The scenario becomes even more compelling as X‐linked TSGs are adaptive to key epigenetic processes such as X chromosome inactivation. Therefore, delineating the new paradigm related to X‐linked TSGs, for instance, their crosstalk with autosome and involvement in cancer initiation, progression, and metastasis becomes utmost importance. Considering this, herein, we present a comprehensive discussion of X‐linked TSG dysregulation in various cancers as a consequence of genetic variations and epigenetic alterations. In addition, the dynamic role of X‐linked TSGs in sex chromosome–autosome crosstalk in cancer genome remodeling is being explored thoroughly. Besides, the functional roles of ncRNAs, role of X‐linked TSG in immunomodulation and in gender‐based cancer disparities has also been highlighted. Overall, the focal idea of the present article is to recapitulate the findings on X‐linked TSG regulation in the cancer landscape and to redefine their role toward improving cancer treatment strategies.

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Section: Tsgs X‐linked Tsgs and Their Involvement In Cancersmentioning

confidence: 85%

Section: And Evolutionary Aspectsmentioning

confidence: 99%

Oncogenes and tumor suppressor genes: functions and roles in cancers

Dakal,

Dhabhai,

Pant

et al. 2024

MedComm

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“…We have previously reported that PPARγ is expressed in UM, which is the most frequent primary intraocular tumor in Caucasian adults with abnormal genetic-epigenetic characteristics and metastatic potential [26,33,34]. Recently, we also reported that DNMT1, along with a few other chromatin-associated genes, is a potential miRNA target cluster embedded within one of the driver genes (BAP1) of UM [26].…”

Section: Discussionmentioning

confidence: 99%

PPAR-Responsive Elements Enriched with Alu Repeats May Contribute to Distinctive PPARγ–DNMT1 Interactions in the Genome

Sharma

Tobar-Tosse

Dakal

et al. 2021

Cancers

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Background: PPARγ (peroxisome proliferator-activated receptor gamma) is involved in the pathology of numerous diseases, including UM and other types of cancer. Emerging evidence suggests that an interaction between PPARγ and DNMTs (DNA methyltransferase) plays a role in cancer that is yet to be defined. Methods: The configuration of the repeating elements was performed with CAP3 and MAFFT, and the structural modelling was conducted with HDOCK. An evolutionary action scores algorithm was used to identify oncogenic variants. A systematic bioinformatic appraisal of PPARγ and DNMT1 was performed across 29 tumor types and UM available in The Cancer Genome Atlas (TCGA). Results: PPAR-responsive elements (PPREs) enriched with Alu repeats are associated with different genomic regions, particularly the promotor region of DNMT1. PPARγ–DNMT1 co-expression is significantly associated with several cancers. C-terminals of PPARγ and DNMT1 appear to be the potential protein–protein interaction sites where disease-specific mutations may directly impair the respective protein functions. Furthermore, PPARγ expression could be identified as an additional prognostic marker for UM. Conclusions: We hypothesize that the function of PPARγ requires an additional contribution of Alu repeats which may directly influence the DNMT1 network. Regarding UM, PPARγ appears to be an additional discriminatory prognostic marker, in particular in disomy 3 tumors.

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“…However, most of studies focused on the gene expression patterns and correlation with the clinical outcomes, mainly survival rate. None of the above-mentioned studies addressed the impact of genome organization in proximity to these genes, which is known to play a pivotal role in human diseases ( 14 ). On this note, the prevalence of repetitive sequences, especially LINEs (Long Interspersed Nuclear Elements), SINEs (Short Interspersed Nuclear Elements), Alu family in the functional parts of genomes and their association with cancers remains undisputed ( 15 – 17 ).…”

Section: Introductionmentioning

confidence: 99%

Systematic discrimination of the repetitive genome in proximity of ferroptosis genes and a novel prognostic signature correlating with the oncogenic lncRNA CRNDE in multiple myeloma

et al. 2022

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Emerging insights into iron-dependent form of regulated cell death ferroptosis in cancer have opened a perspective for its use in cancer therapy. Of interest, a systematic profiling of ferroptosis gene signatures as prognostic factors has gained special attention in several cancers. Herein, we sought to investigate the presence of repetitive genomes in the vicinity of ferroptosis genes that may influence their expression and to establish a prognostic gene signature associated with multiple myeloma (MM). Our analysis showed that genes associated with ferroptosis were enriched with the repetitive genome in their vicinity, with a strong predominance of the SINE family, followed by LINE, of which the most significant discriminant values were SINE/Alu and LINE/L1, respectively. In addition, we examined in detail the performance of these genes as a cancer risk prediction model and specified fourteen ferroptosis-related gene signatures, which identified MM high-risk patients with lower immune/stromal scores with higher tumor purity in their immune microenvironment. Of interest, we also found that lncRNA CRNDE correlated with a risk score and was highly associated with the majority of genes comprising the signature. Taken together, we propose to investigate the molecular impact of the repetitive genome we have highlighted on the local transcriptome of ferroptosis genes in cancer. Furthermore, we revealed a genomic signature/biomarker related to ferroptosis that can be used to predict the risk of survival in MM patients.

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Genome organization in proximity to the BAP1 locus appears to play a pivotal role in a variety of cancers

Cited by 11 publications

References 38 publications

Oncogenes and tumor suppressor genes: functions and roles in cancers

Oncogenes and tumor suppressor genes: functions and roles in cancers

PPAR-Responsive Elements Enriched with Alu Repeats May Contribute to Distinctive PPARγ–DNMT1 Interactions in the Genome

Systematic discrimination of the repetitive genome in proximity of ferroptosis genes and a novel prognostic signature correlating with the oncogenic lncRNA CRNDE in multiple myeloma

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