The regulatory role of MiR-203 in oxidative stress induced cell injury through the CBS/H2S pathway

Zhang, Qiuyan; Shen, Zhuqing; Shen, Yaqi; Ma, Muye; Jue, Hao; Zhu, Yizhun; Wei, Guo

doi:10.1016/j.niox.2021.10.007

Cited by 7 publications

(4 citation statements)

References 25 publications

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“…MicroRNA (miR) and transcription factors can also act as direct regulators of H 2 S synthases. MiR‐24‐3p, miR‐203, and miR‐376a can target CBS to induce apoptosis, and miR‐559 can also target CBS to inhibit cell proliferation 130,138,173,174 . MiR‐30 family can induce oxidative stress by inhibiting CSE, 175,176 while miR‐216a also directly targeted CSE to inhibit its expression 177 .…”

Section: Methods For Inhibiting Endogenous H2smentioning

confidence: 99%

“…MiR-24-3p, miR-203, and miR-376a can target CBS to induce apoptosis, and miR-559 can also target CBS to inhibit cell proliferation. 130,138,173,174 MiR-30 family can induce oxidative stress by inhibiting CSE, 175,176 while miR-216a also directly targeted CSE to inhibit its expression. 177 And miR-4137 can inhibit both CBS and CSE in BC to yield a tumour-suppressing effect.…”

Section: Microrna and Transcription Factorsmentioning

confidence: 99%

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Recent advances in the role of endogenous hydrogen sulphide in cancer cells

Chen

Qin

et al. 2023

Cell Proliferation

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Hydrogen sulphide (H2S) is a gaseous neurotransmitter that can be self‐synthesized by living organisms. With the deepening of research, the pathophysiological mechanisms of endogenous H2S in cancer have been increasingly elucidated: (1) promote angiogenesis, (2) stimulate cell bioenergetics, (3) promote migration and proliferation thereby invasion, (4) inhibit apoptosis and (5) activate abnormal cell cycle. However, the increasing H2S levels via exogenous sources show the opposite trend. This phenomenon can be explained by the bell‐shaped pharmacological model of H2S, that is, the production of endogenous (low concentration) H2S promotes tumour growth while the exogenous (high concentration) H2S inhibits tumour growth. Here, we review the impact of endogenous H2S synthesis and metabolism on tumour progression, summarize the mechanism of action of H2S in tumour growth, and discuss the possibility of H2S as a potential target for tumour treatment.

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Section: Methods For Inhibiting Endogenous H2smentioning

confidence: 99%

Section: Microrna and Transcription Factorsmentioning

confidence: 99%

Recent advances in the role of endogenous hydrogen sulphide in cancer cells

Chen

Qin

et al. 2023

Cell Proliferation

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“…The expression profiles of miRNAs that target H 2 S-synthesizing enzymes, have been found to be altered in different clinical oncological and non-oncological settings. MiR-203 has been found to regulate oxidative stress induced cell injury by regulating CBS expression and adjusting the levels of H 2 S production [ 27 ]. In colorectal cancer, miR-559 was shown to target CBS thus reducing the accelerated cancer cell proliferation [ 28 ].…”

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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“…neurodegenerative diseases [5], aging [6] and schizophrenia [7]. Among these RSS molecules, H 2 S is the third gas signal molecule with biological activity after NO and CO, which has been extensively studied in recent years [8][9][10][11]. With further research, H 2 S n (n>1) has been found to be more effective than H 2 S in adjusting the activities of ion channels, transcription factors, protein kinases and tumor suppressors [12,13].…”

Section: Introductionmentioning

confidence: 99%