Circular and linear: a tale of aptamer selection for the activation of SIRT1 to induce death in cancer cells

Al-Sudani, Basma Talib; Ragazzon-Smith, Abby; Aziz, Athar; Alansari, Rania; Ferry, Nicolas; Krstic‐Demonacos, Marija; Ragazzon, Patricia A.

doi:10.1039/d0ra07857c

Cited by 4 publications

(6 citation statements)

References 73 publications

(86 reference statements)

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“…The results also revealed in current study that SIRT1 protects human corneal epithelial 2.040 pRSV-T cells from oxidative stress by blocking the p53 pathway. Apoptosis is triggered by the protein p53, 14,15 and it has been demonstrated that P53 is a SIRT1 substrate. 20,21 The p53 protein is involved in cellular responses to a wide range of stressors, including DNA damage, hypoxia, and oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

SIRT1720 promotes survival of corneal epithelial cells via the P53 pathway

Jalil

Al-Sudani

Jasim

2022

JPTCP

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Purpose: To investigate the protective role of SRT1720 (SIRT1 activator) against the oxidative stress caused by H 2 O 2 in the corneal cell line. Methods: Human corneal (2.040 pRSV-T) cell lines were cultured and treated with SRT1720 (as SIRT1 activator) and nicotinamide (NAM, a SIRT1 inhibitor), and incubated with H 2 O 2 . The expression level of SIRT1, p53, and acetyl-p53 was measured by western blot. Propidium iodine/annexin V-FITC staining, and flow cytometry was used to evaluate apoptosis. The trypan blue assay was used to assess the morphological modifications that occurred after the treatment, and Pifithrin-α (PFT-α) was used to inhibit the p53 pathway. Results:The investigation revealed that under oxidative stress, SRT1720 caused a reduction in acetyl-p53 expression and increased SIRT1 expression. It was also found that under oxidative stress, SRT1720 suppressed apoptosis. In comparison, NAM promoted cell apoptosis under oxidative stress. NAM's destructive effect was eliminated by PFT-α, a suppressor of the p53 pathway. PFT-α reduced the morphological changes in 2.040 pRSV-T cell lines compared to NAM treatment and inhibited apoptosis. Conclusions: The protective effects of the SIRT1 activator (SRT1720) indicate that H 2 O 2 induces oxidative stress-associated cell damage. The results also encouraged us to consider using SRT1720 to improve corneal safety and reduce the adverse effects of oxidative damage.

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Section: Discussionmentioning

confidence: 99%

SIRT1720 promotes survival of corneal epithelial cells via the P53 pathway

Jalil

Al-Sudani

Jasim

2022

JPTCP

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“…RNA aptamers and RNA aptamer-based devices can be genetically encoded and expressed in cells to probe and regulate cellular function. 50 Because aptamers can bind specific domains and conformations of proteins, 51 they can either inhibit proteins or modulate their function. Circular RNA can be used as RNA aptamer.…”

Section: Application Of Circrna In the Diagnosis And Treatment Of Ost...mentioning

confidence: 99%

“…The study of Al-Sudani et al 50 proved that there are two types of aptamer selection, circular and linear. AC3, a circular aptamer, stood up as the optimal aptamer for inducing SIRT1 activity and exerting anticancer action.…”

Section: Application Of Circrna In the Diagnosis And Treatment Of Ost...mentioning

confidence: 99%

Recent Advances of Circular RNAs as Biomarkers for Osteosarcoma

Wu¹,

Zheng²,

He³

et al. 2023

IJGM

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Osteosarcoma is the most common primary malignant bone tumor in young adult, which is prone to early metastasis and poor prognosis. The current treatment methods need to be improved. Circular RNA is a covalently blocked circular, non-coding RNA that plays an essential role in the occurrence, development, clinical diagnosis, and treatment of various diseases. Recently, an increasing number of circRNAs have been identified in osteosarcoma. Understanding its role in osteosarcoma is conducive to the early detection, diagnosis, and treatment of osteosarcoma. In this paper, we reviewed the mechanism of action of circular RNA in the occurrence and development of osteosarcoma and its clinical application in recent years.

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“…Accordingly, we hypothesize that SIRT1 aptamer (as SIRT1 activator) could exert its protective actions through reducing the abnormal increase in the level of NO following exposure to ultraviolet radiation. SIRT1 aptamer is a novel SIRT1 ligands (DNA sequences consist of 40 nucleotides) that bind and modulate the activity of SIRT1 within cells and enhance its enzymatic activity which is used NAD+ to remove acetyl groups from proteins (5).…”

Section: Cellularmentioning

confidence: 99%

“…In addition to that, SIRT1 aptamer was tested for both cancer and normal cells and SIRT1 aptamer show selected activity against cancer cells that had elevated level of SIRT1 and this selectivity is absent in Resveratrol and the SIRT1 activators compounds. This means; SIRT1 aptamer has the advantage over chemotherapy in selectivity against cancer cells with high limitation of adverse effects associated with chemotherapy (5,13). In toxicology studies, neither activation of the immune system, nor complement activation by SIRT1 aptamer was reported.…”

Section: Figurementioning

confidence: 99%

Protective Action of SIRT1 Activator Aptamer in Human Skin Cell Line

2023

JPTCP

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The skin is the largest organ of the body. The general aging process, which is genetically fixed and happens solely with the passage of time, is referred to as the intrinsic skin aging process. The skin aging process caused by external causes is referred to as extrinsic skin aging. The skin must endure a continual bombardment from the outside by reactive oxygen species, or ROS, which are given to the skin by the environment and created within the skin itself, either as a reaction to incoming UV radiation or made when mitochondria aerobic respiration. An increase in the levels of ROS lead to damage the mtDNA, affecting cell signaling and inducing the apoptosis responses, such as senescence, fibrosis, calcification, and hypertrophy. During the past decade, investigators have reported the relationship between disturbance of SIRT1 activation and the onset of aging. Sirtuin1 is indispensable for DNA repair which make it good anti-senescence/anti-ageing targets and because ROS and SIRT1 are disturbed in the aging process. Because of its enhancing effect on reactive oxygen species and apoptotic pathways, an aberrant increase in NO generation has been linked to early skin aging. We'll look at how SIRT1 aptamer (as a SIRT1 activator) can protect cells against sodium nitroprussideinduced cell death (SNP), employing a human keratinocyte cell line to study a well-known NO generating chemical with suspected harmful and apoptotic effects on keratinocytes (HaCaT). As a result, the primary goal of this research is to discover and define the protective effects of SIRT1 activators in human skin cells. Finally, the findings imply that SIRT1 aptamer might be effective in preventing skin aging caused by reactive oxygen species (ROS).

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Circular and linear: a tale of aptamer selection for the activation of SIRT1 to induce death in cancer cells

Abstract: We report novel SIRT1 ligands that bind and modulate the activity of SIRT1 within cells and enhance its enzymatic activity. From a pool of aptamers we identify circular AC3 as having anticancer activity.

Cited by 4 publications

References 73 publications

SIRT1720 promotes survival of corneal epithelial cells via the P53 pathway

SIRT1720 promotes survival of corneal epithelial cells via the P53 pathway

Recent Advances of Circular RNAs as Biomarkers for Osteosarcoma

Protective Action of SIRT1 Activator Aptamer in Human Skin Cell Line

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