60P Curbing the interplay between miR-939-5p and HEIH lncRNA by EGCG represses hydrogen sulphide machinery and hinders breast cancer progression

Nafea, Heba; Youness, R.A.; Abou-Aisha, Khaled

doi:10.1016/j.annonc.2020.08.2219

Cited by 4 publications

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“…Several studies have shown that human breast cancer tissues and cells lines (MDA-MB-468, MCF-7, and Hs578T) reveal the marked overexpression of CBS, CSE, and 3MST compared to normal breast cells [ 31 , 132 , 180 ]. Recently, our research group has highlighted the potential regulation of CBS and CSE in breast cancer cell lines by miR-4317 [ 31 ] and miR-939-5p [ 181 , 182 ]. It is worth mentioning that, recently, miR-548 and miR-193 have been found by our research group to simultaneously target the three synthesizing enzymes in breast cancer: CBS, CSE and 3MST ( Table 2 ) [ 132 , 183 ].…”

Section: Role Of H 2 S In Oncological Disorders An...mentioning

confidence: 99%

Role of Hydrogen Sulfide in Oncological and Non-Oncological Disorders and Its Regulation by Non-Coding RNAs: A Comprehensive Review

Youness,

Habashy,

Khater

et al. 2024

ncRNA

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Recently, myriad studies have defined the versatile abilities of gasotransmitters and their synthesizing enzymes to play a “Maestro” role in orchestrating several oncological and non-oncological circuits and, thus, nominated them as possible therapeutic targets. Although a significant amount of work has been conducted on the role of nitric oxide (NO) and carbon monoxide (CO) and their inter-relationship in the field of oncology, research about hydrogen sulfide (H2S) remains in its infancy. Recently, non-coding RNAs (ncRNAs) have been reported to play a dominating role in the regulation of the endogenous machinery system of H2S in several pathological contexts. A growing list of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are leading the way as upstream regulators for H2S biosynthesis in different mammalian cells during the development and progression of human diseases; therefore, their targeting can be of great therapeutic benefit. In the current review, the authors shed the light onto the biosynthetic pathways of H2S and their regulation by miRNAs and lncRNAs in various oncological and non-oncological disorders.

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Section: Role Of H 2 S In Oncological Disorders An...mentioning

confidence: 99%

Role of Hydrogen Sulfide in Oncological and Non-Oncological Disorders and Its Regulation by Non-Coding RNAs: A Comprehensive Review

Youness,

Habashy,

Khater

et al. 2024

ncRNA

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“…In recent years, extensive research has been carried out to determine the role of H 2 S in immunomodulation and in tumor immune microenvironment (TIME) [ 12 ]. Regulators of H 2 S-synthesizing machinery and H 2 S intracellular levels have been reported to modulate the TIME [ 13 – 15 ]. In a study conducted by our group, where BC cells were co-cultured with natural killer (NK) cells, the decrease of either CBS-derived or CSE-derived H 2 S has led to an increase in NK cell-mediated catalytic activity [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

“…Regulators of H 2 S-synthesizing machinery and H 2 S intracellular levels have been reported to modulate the TIME [ 13 – 15 ]. In a study conducted by our group, where BC cells were co-cultured with natural killer (NK) cells, the decrease of either CBS-derived or CSE-derived H 2 S has led to an increase in NK cell-mediated catalytic activity [ 15 ]. Moreover, CBS-derived H 2 S has exerted immunosuppressive activity by protecting BC cells from activated macrophage-generated ROS in macrophage-BC cell co-cultures [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Pan-inhibition of the three H2S synthesizing enzymes restrains tumor progression and immunosuppression in breast cancer

Dawoud,

Youness,

Nafea

et al. 2024

Cancer Cell Int

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Background Hydrogen sulfide (H2S) is a significant endogenous mediator that has been implicated in the progression of various forms of cancer including breast cancer (BC). Cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3MST) are the three principal mammalian enzymes responsible for H2S production. Overexpression of CBS, CSE and 3MST was found to be associated with poor prognosis of BC patients. Moreover, H2S was linked to an immune-suppressive tumor microenvironment in BC. Recently it was observed that BC cells, in response to single or dual inhibition of H2S synthesizing enzymes, develop an escape mechanism by overexpressing alternative sources of H2S generation. Thus, the aim of this work is to escape the H2S compensatory mechanism by pan repressing the three enzymes using microRNAs (miRNAs) and to investigate their impact on the oncogenic and immunogenic profile of BC cells. Methods BC female patients (n = 25) were recruited. In-silico analysis was used to identify miRNAs targeting CBS, CSE, and 3MST. MDA-MB-231 cells were cultured and transfected using oligonucleotides. Total RNA was extracted using Biazol, reverse transcribed and quantified using qRT-PCR. H2S levels were measured using AzMc assay. BC hallmarks were assessed using trans-well migration, wound healing, MTT, and colony forming assays. Results miR-193a and miR-548c were validated by eight different bioinformatics software to simultaneously target CBS, CSE and 3MST. MiR-193a and miR-548c were significantly downregulated in BC tissues compared to their non-cancerous counterparts. Ectopic expression of miR-193a and miR-548c in MDA-MB-231 TNBC cells resulted in a marked repression of CBS, CSE, and 3MST transcript and protein levels, a significant decrease in H2S levels, reduction in cellular viability, inhibition of migration and colony forming ability, repression of immune-suppressor proteins GAL3 GAL9, and CD155 and upregulation of the immunostimulatory MICA and MICB proteins. Conclusion This study sheds the light onto miR-193a and miR-548c as potential pan-repressors of the H2S synthesizing enzymes. and identifies them as novel tumor suppressor and immunomodulatory miRNAs in TNBC.

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“…Many of the genes that include ncRNAs are evolutionarily conserved, much like protein‐coding genes, and have been connected to a variety of biological processes that impact development, differentiation, and several aspects of cellular physiology (Youness & Gad, 2019). It is becoming obvious that abnormal ncRNAs expression is frequently seen in several cancers (Abdallah et al, 2022; Awad et al, 2021; El Din et al, 2021; El Kilany et al, 2021; Fahmy, Dawoud, et al, 2022; Mekky et al, 2023; Nafea et al, 2020; Ramzy et al, 2022; Shaalan et al, 2018; Youness, Rahmoon, et al, 2016; Youness et al, 2018, 2019, 2021, 2022; ZeinElAbdeen et al, 2022), indicating that ncRNAs are important participants in human carcinogenesis (Abdel‐Latif et al, 2022; Ahmed Youness et al, 2020; ElKhouly et al, 2020; Fahmy, Dawoud, et al, 2022; Mekky et al, 2019; Nafea et al, 2021; Soliman et al, 2022; Youssef et al, 2022; ZeinElAbdeen et al, 2022). Recent evidence suggests that these evolutionarily conserved ncRNAs, notably long noncoding RNAs (lncRNAs), PIWI‐interacting RNAs (piRNAs), and circular RNAs (circRNAs), play a significant role in a variety of physiological and pathological processes (Dawoud et al, 2023; Selem et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Decoding hepatocarcinogenesis from a noncoding RNAs perspective

El-Aziz

Dawoud

Kiriacos

et al. 2023

Journal Cellular Physiology

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Being a leading lethal malignancy worldwide, the pathophysiology of hepatocellular carcinoma (HCC) has gained a lot of interest. Yet, underlying mechanistic basis of the liver tumorigenesis is poorly understood. The role of some coding genes and their respective translated proteins, then later on, some noncoding RNAs (ncRNAs) such as microRNAs have been extensively studied in context of HCC pathophysiology; however, the implication of long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) in HCC is indeed less investigated. As a subclass of the ncRNAs which has been elusive for long time ago, lncRNAs was found to be involved in plentiful cellular functions such as DNA, RNA, and proteins regulation. Hence, it is undisputed that lncRNAs dysregulation profoundly contributes to HCC via diverse etiologies. Accordingly, lncRNAs represent a hot research topic that requires prime focus in HCC. In this review, the authors discuss breakthrough discoveries involving lncRNAs and circRNAs dysregulation that have contributed to the contemporary concepts of HCC pathophysiology and how these concepts could be leveraged as potential novel diagnostic and prognostic HCC biomarkers. Further, this review article sheds light on future trends, thereby discussing the pathological roles of lncRNAs and circRNAs in HCC proliferation, migration, and epithelial‐to‐mesenchymal transition. Along this line of reasoning, future recommendations of how these targets could be exploited to achieve effective HCC‐related drug development is highlighted.

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60P Curbing the interplay between miR-939-5p and HEIH lncRNA by EGCG represses hydrogen sulphide machinery and hinders breast cancer progression

Cited by 4 publications

References 0 publications

Role of Hydrogen Sulfide in Oncological and Non-Oncological Disorders and Its Regulation by Non-Coding RNAs: A Comprehensive Review

Role of Hydrogen Sulfide in Oncological and Non-Oncological Disorders and Its Regulation by Non-Coding RNAs: A Comprehensive Review

Pan-inhibition of the three H2S synthesizing enzymes restrains tumor progression and immunosuppression in breast cancer

Decoding hepatocarcinogenesis from a noncoding RNAs perspective

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