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Mechanism of hydrogen on cervical cancer suppression revealed by high‑throughput RNA sequencing.

ABSTRACT: Cervical cancer is considered one of the diseases with the highest mortality among women and with limited treatment options. Hydrogen (H₂) inhalation has been reported to have a variety of tumor‑suppressive effects, but the exact mechanism remains unclear. In the present study, HeLa cervical cancer cells and HaCaT keratinocytes treated with H₂, and a HeLa xenograft mouse model subjected to H₂ inhalation were established. TUNEL, Cell Counting Kit‑8 and Ki67 staining assays were used to detect cell apoptosis and proliferation. Oxidative stress was determined according to the levels of reactive oxygen species, malondialdehyde and superoxide dismutase. Tumor growth was recorded every 3 days, and the excised tumors were stained with hematoxylin and eosin. High‑throughput RNA sequencing and subsequent Gene Ontology (GO) enrichment analysis were performed in HeLa‑treated and un‑treated HeLa cells. The expression of hypoxia‑inducible factor (HIF)‑1α and NF‑κB p65 was verified by western blotting, immunohistochemistry and reverse transcription‑quantitative PCR. The results revealed an increased apoptosis rate, and reduced cell proliferation and oxidative stress in H₂‑treated HeLa cells but not in HaCaT cells. Similarly, decreased tumor growth and cell proliferation, and enhanced cell apoptosis were observed in H2‑treated HeLa tumors. RNA sequencing and GO analysis suggest that downregulated HIF1A (HIF‑1α mRNA) and RelA (NF‑κB p65) levels, and reduced NF‑κB signaling were associated with the antitumor effect of H₂. Finally, decreased HIF‑1α and NF‑κB p65 expression both at the transcriptional and translational levels were observed in H₂‑treated HeLa cells and in HeLa‑derived tumors. In conclusion, the present study reveals a novel mechanism of H₂ against cervical cancer, which may serve as a potential therapeutic target in clinical practice.

SUBMITTER: Chu J

PROVIDER: S-EPMC8165587 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Clinical interpretation of the large number of rare variants identified by high throughput sequencing (HTS) technologies is challenging. The aim of this study was to explore the clinical implications of a HTS strategy for patients with hypertrophic cardiomyopathy (HCM) using a targeted HTS methodology and workflow developed for patients with a range of inherited cardiovascular diseases. By comparing the sequencing results with published findings and with sequence data from a large-scale exome sequencing screen of UK individuals, we sought to quantify the strength of the evidence supporting causality for detected candidate variants. METHODS AND RESULTS:223 unrelated patients with HCM (46±15 years at diagnosis, 74% males) were studied. In order to analyse coding, intronic and regulatory regions of 41 cardiovascular genes, we used solution-based sequence capture followed by massive parallel resequencing on Illumina GAIIx. Average read-depth in the 2.1 Mb target region was 120. Rare (frequency<0.5%) non-synonymous, loss-of-function and splice-site variants were defined as candidates. Excluding titin, we identified 152 distinct candidate variants in sarcomeric or associated genes (89 novel) in 143 patients (64%). Four sarcomeric genes (MYH7, MYBPC3, TNNI3, TNNT2) showed an excess of rare single non-synonymous single-nucleotide polymorphisms (nsSNPs) in cases compared to controls. The estimated probability that a nsSNP in these genes is pathogenic varied between 57% and near certainty depending on the location. We detected an additional 94 candidate variants (73 novel) in desmosomal, and ion-channel genes in 96 patients (43%). CONCLUSIONS:This study provides the first large-scale quantitative analysis of the prevalence of sarcomere protein gene variants in patients with HCM using HTS technology. Inclusion of other genes implicated in inherited cardiac disease identifies a large number of non-synonymous rare variants of unknown clinical significance.

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Mechanism of hydrogen on cervical cancer suppression revealed by high‑throughput RNA sequencing.

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