Development of omics biomarkers for estrogen exposure using mRNA, miRNA and piRNAs

Toth, Gregory P.; Bencic, David C.; Martinson, John; Flick, Robert W.; Lattier, David L.; Kostich, Mitchell S.; Huang, Weichun

doi:10.1016/j.aquatox.2021.105807

Cited by 6 publications

(6 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…No differentially expressed miRNA genes were detected at an FDR of 0.05, suggesting that propranolol does not alter sncRNA transcriptional levels. This result mirrors that of another one of our recent FHM larval studies (Toth et al, 2021), where small‐RNA‐seq analyses showed no significantly affected miRNA following ethinylestradiol exposure. Given that these are the only two studies to evaluate sncRNA expression in FHM, it is possible that negative results reflect the immaturity of the FHM miRNAome or may result from the use of whole organisms and the averaging of tissue‐specific miRNA levels across tissues.…”

Section: Resultssupporting

confidence: 89%

Effects of Age and Exposure Duration on the Sensitivity of Early Life Stage Fathead Minnow (Pimephales promelas) to Waterborne Propranolol Exposure

Biales,

Bencic,

Flick

et al. 2024

Enviro Toxic and Chemistry

Self Cite

View full text Add to dashboard Cite

Propranolol is a heavily prescribed, non‐specific beta‐adrenoceptor (bAR) antagonist frequently found in wastewater effluents, prompting concern over its potential to adversely affect exposed organisms. Herein, the transcriptional responses of 4, 5, and 6 dpf +/‐ 1h fathead minnow (FHM), exposed for 6, 24, or 48hr to 0.66 or 3.3mg/L (nominal) propranolol were characterized using RNA‐seq. The number of differentially expressed genes (DEGs) was used as an estimate of sensitivity. A trend toward increased sensitivity with age was observed; fish >7dpf at the end of exposure were particularly sensitive to propranolol. DEGs largely overlapped among treatment groups, suggesting a highly consistent response that was independent of age. Cluster analysis was performed using normalized count data for unexposed and propranolol exposed fish. Control fish clustered tightly by age, with fish >= 7dpf clustering away from younger fish, reflecting developmental differences. When clustering was conducted using exposed fish, in cases where propranolol induced a minimal or no transcriptional response, results mirrored those of the control fish and did not appreciably cluster by treatment. In treatment groups that displayed a more robust transcriptional response, the effects of propranolol were evident, however, fish < 7dpf clustered away from older fish, despite having similar numbers of DEGs. Increased sensitivity at 7dpf coincided with developmental milestones with the potential to alter propranolol pharmacokinetics or pharmacodynamics, such as the onset of exogenous feeding and gill functionality, as well as increased systemic expression of bAR. These results may have broader implications, as toxicity testing often utilizes fish < 4dpf, prior to the onset of these potentially important developmental milestones, which may result in an underestimation of risk for some chemicals.

show abstract

Section: Resultssupporting

confidence: 89%

Effects of Age and Exposure Duration on the Sensitivity of Early Life Stage Fathead Minnow (Pimephales promelas) to Waterborne Propranolol Exposure

Biales,

Bencic,

Flick

et al. 2024

Enviro Toxic and Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…92 c. Epigenetic Regulation: PiRNAs actively participate in epigenetic regulation, a mechanism capable of inducing enduring alterations in gene expression patterns. 93 This epigenetic influence may confer a sustained and resilient response to ICI therapy, surpassing the capabilities of microRNAs. d. Germline Resilience: PiRNAs are celebrated for their stability across generations, serving as custodians of germline integrity.…”

Section: Pirnasmentioning

confidence: 99%

“…d. Germline Resilience: PiRNAs are celebrated for their stability across generations, serving as custodians of germline integrity. 93 This exceptional stability could translate into prolonged effects within cells, potentially leading to an enduring and sustained immune response against cancerous cells, by choosing proper piRNAs. e. Potential for Transgenerational Impact: In select organisms, piRNAs have shown the intriguing ability to traverse generational boundaries.…”

Section: Pirnasmentioning

confidence: 99%

Synergistic Immunoregulation: harnessing CircRNAs and PiRNAs to Amplify PD-1/PD-L1 Inhibition Therapy

Han,

Rao,

Zhou

et al. 2024

IJN

View full text Add to dashboard Cite

The utilization of PD-1/PD-L1 inhibitors marks a significant advancement in cancer therapy. However, the efficacy of monotherapy is still disappointing in a substantial subset of patients, necessitating the exploration of combinational strategies. Emerging from the promising results of the KEYNOTE-942 trial, RNA-based therapies, particularly circRNAs and piRNAs, have distinguished themselves as innovative sensitizers to immune checkpoint inhibitors (ICIs). These non-coding RNAs, notable for their stability and specificity, were once underrecognized but are now known for their crucial roles in regulating PD-L1 expression and bolstering anti-cancer immunity. Our manuscript offers a comprehensive analysis of selected circRNAs and piRNAs, elucidating their immunomodulatory effects and mechanisms, thus underscoring their potential as ICIs enhancers. In conjunction with the recent Nobel Prize-awarded advancements in mRNA vaccine technology, our review highlights the transformative implications of these findings for cancer treatment. We also discuss the prospects of circRNAs and piRNAs in future therapeutic applications and research. This study pioneers the synergistic application of circRNAs and piRNAs as novel sensitizers to augment PD-1/PD-L1 inhibition therapy, demonstrating their unique roles in regulating PD-L1 expression and modulating immune responses. Our findings offer a groundbreaking approach for enhancing the efficacy of cancer immunotherapy, opening new avenues for treatment strategies. This abstract aims to encapsulate the essence of our research and the burgeoning role of these non-coding RNAs in enhancing PD-1/ PD-L1 inhibition therapy, encouraging further investigation into this promising field.

show abstract

“…Due to miRNA versatility and the growing body of toxicological research, routine evaluation of miRNA biomarker detection methods and regulatory mechanisms is required to advance future miRNA research. To date, piRNA biomarkers have been discovered from cell lines and multiple species in response to ethinylestradiol, 242 fluoride, 243 tetrabromodiphenyl ether (DBE-47), 182 cigarette smoke, 244 dichlorodiphenyltrichloroethane, 245 and diseases. 246,247 circRNA biomarkers are emerging players in toxicological research.…”

Section: Informationmentioning

confidence: 99%

Toxicoepigenetics and Environmental Health: Challenges and Opportunities

Svoboda

Perera

Morgan

et al. 2022

Chem. Res. Toxicol.

View full text Add to dashboard Cite

The rapidly growing field of toxicoepigenetics seeks to understand how toxicant exposures interact with the epigenome to influence disease risk. Toxicoepigenetics is a promising field of environmental health research, as integrating epigenetics into the field of toxicology will enable a more thorough evaluation of toxicant-induced disease mechanisms as well as the elucidation of the role of the epigenome as a biomarker of exposure and disease and possible mediator of exposure effects. Likewise, toxicoepigenetics will enhance our knowledge of how environmental exposures, lifestyle factors, and diet interact to influence health. Ultimately, an understanding of how the environment impacts the epigenome to cause disease may inform risk assessment, permit noninvasive biomonitoring, and provide potential opportunities for therapeutic intervention. However, the translation of research from this exciting field into benefits for human and animal health presents several challenges and opportunities. Here, we describe four significant areas in which we see opportunity to transform the field and improve human health by reducing the disease burden caused by environmental exposures. These include (1) research into the mechanistic role for epigenetic change in environment-induced disease, (2) understanding key factors influencing vulnerability to the adverse effects of environmental exposures, (3) identifying appropriate biomarkers of environmental exposures and their associated diseases, and (4) determining whether the adverse effects of environment on the epigenome and human health are reversible through pharmacologic, dietary, or behavioral interventions. We then highlight several initiatives currently underway to address these challenges.

show abstract

Development of omics biomarkers for estrogen exposure using mRNA, miRNA and piRNAs

Cited by 6 publications

References 69 publications

Effects of Age and Exposure Duration on the Sensitivity of Early Life Stage Fathead Minnow (Pimephales promelas) to Waterborne Propranolol Exposure

Effects of Age and Exposure Duration on the Sensitivity of Early Life Stage Fathead Minnow (Pimephales promelas) to Waterborne Propranolol Exposure

Synergistic Immunoregulation: harnessing CircRNAs and PiRNAs to Amplify PD-1/PD-L1 Inhibition Therapy

Toxicoepigenetics and Environmental Health: Challenges and Opportunities

Contact Info

Product

Resources

About