TOXICOLOGY LETTERS
·
2025
·
IF 2.9
Zhongming Ye,Qihao Huang,Haipeng Wu,Shimei Wang,Boxin Li,Minjuan Zeng,Tikeng Jiang,Biyan Ye,Yixian Wei,Lei Sun,Shaoying Wang,Yutao Zeng,Yuting Chen,Huanwen Tang
Benzene, a recognized carcinogen, is utilized in synthesizing various chemicals. Epidemiological studies have established a positive correlation between benzene exposure and increased incidences of abnormal menstruation and dysmenorrhea. This exposure might also pose risks to the fetal hematopoietic system. However, the precise molecular mechanisms underlying these effects are not fully understood. In this study, a chronic benzene exposure model was established through dynamic inhalation. We assessed the autophagy levels in mouse ovarian granulosa cells and human ovarian granulosa cells treated with 1,4-benzoquinone using molecular biology techniques such as qPCR, Western blot, and transmission electron microscopy (TEM), etc. The experimental results show that Benzene-exposed mice exhibited autophagy, a reduced number of ovarian granulosa cells, and vacuolar lesions in the fallopian tubes. Cell-based experiments demonstrated that benzene exposure significantly upregulated SNHG15 expression in human ovarian granulosa cells ( P < 0.05). The upregulation of SNHG15 enhanced FOXO3 expression via the miR-3143/FOXO3 axis, which in turn increased the transcription of autophagy-related proteins such as Atg5 ( P < 0.05), ultimately leading to excessive autophagy in granulosa cells and ovarian dysfunction. Benzene and its metabolite benzoquinone increase autophagy in ovarian granulosa cells. The lncRNA SNHG15 regulates this autophagy induced by benzene exposure through sponge-like binding to miR-3143/FOXO3, thus impairing ovarian function. Inhibiting SNHG15, miR-3143, and FOXO3 expression markedly reduced autophagy in granulosa cells and ameliorated ovarian dysfunction resulting from benzene exposure. These results suggest that the ceRNA axis involving SNHG15 may be a potential clinical therapeutic target.
研究领域:
毒理学
·
分子生物学
·
遗传学
·
生殖生物学
·
环境卫生
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Heart Journal
·
2022
·Vol. 63
·期 3
·578-590
·
IF 1.823
Haibo Du,Lianqin Ding,Tian Zeng,Di Li,Li Liu
Myocardial ischemia-reperfusion (I/R) injury is a serious complication of acute myocardial infarction. Long noncoding RNA (lncRNA) small nucleolar RNA host gene 15 (SNHG15) can regulate I/R-induced cardiomyocyte apoptosis. Here, we investigated the mechanism of SNHG15 activity in I/R-induced cardiomyocyte injury.SNHG15, microRNA (miR)-335-3p, and toll-like receptor 4 (TLR4) were quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Cell viability, proliferation, and apoptosis were gauged by Cell Counting Kit-8 (CCK-8) assay, 5-ethynyl-2´-deoxyuridine (EDU) assay, and flow cytometry, respectively. The direct relationship between miR-335-3p and SNHG15 or TLR4 was validated by dual-luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays.SNHG15 was overexpressed in the infarcted area tissues of I/R mice and I/R-stimulated AC16 cells. SNHG15 knockdown alleviated I/R injury in AC16 cells. Mechanistically, SNHG15 directly targeted miR-335-3p, and miR-335-3p was a functional mediator of SNHG15. MiR-335-3p inhibited TLR4 expression by targeting TLR4, and miR-335-3p-mediated inhibition of TLR4 alleviated I/R-induced injury in AC16 cells. Moreover, SNHG15 regulated the TLR4/nuclear factor-κB (NF-κB) signaling pathway through miR-335-3p.Our findings identify a novel mechanism, the miR-335-3p/TLR4/NF-κB pathway, for the regulation of SNHG15 in myocardial I/R injury.
研究领域:
分子生物学
·
心脏病学
·
细胞生物学
✓ 已验证
产品关联
DOI
高影响因子
YONSEI MEDICAL JOURNAL
·
2021
·
IF 2.759
Chunting Hu,Chen Li,Qiaoya Ma,Ruili Wang,Ya He,Hui Wang,Guogang Luo
Purpose Ischemic brain injury results in high mortality and serious neurologic morbidity. Here, we explored the role of SNHG15 in modulating neuronal damage and microglial inflammation after ischemia stroke. Materials and Methods The hypoxia/ischemia models were induced by middle cerebral artery occlusion in mice and oxygen-glucose deprivation/reoxygenation (OGD/R) in vitro. Quantitative real-time PCR (qRT-PCR) and Western blot were conducted to determine the levels of SNHG15, miR-302a-3p, and STAT1/NF-κB. Moreover, gain- or loss-of functional assays of SNHG15 and miR-302a-3p were conducted. MTT assay was used to evaluate the viability of HT22 cells, and the apoptotic level was determined by flow cytometry. Furthermore, enzyme-linked immunosorbent assay was performed to detect oxidative stress and inflammatory mediators in the ischemia cortex and OGD/R-treated BV2 microglia. Results The SNHG15 and STAT1/NF-κB pathways were both distinctly up-regulated, while miR-302a-3p was notably down-regulated in the ischemia cortex. Additionally, overexpressing SNHG15 dramatically enhanced OGD/R-mediated neuronal apoptosis as well as the expression of oxidative stress and inflammation factors from microglia. In contrast, knocking down SNHG15 or overexpressing miR-302a-3p relieved OGD/R-mediated neuronal apoptosis and microglial activation. Moreover, the rescue experiment testified that overexpressing miR-302a-3p also attenuated SNHG15 up-regulation-induced effects. In terms of the mechanisms, SNHG15 sponged miR-302a-3p and activated STAT1/NF-κB as a competitive endogenous RNA, while miR-302a-3p targeted STAT1 and negatively regulated the STAT1/NF-κB pathway. Conclusion SNHG15 was up-regulated in the hypoxia/ischemia mouse or cell model. The inhibition of SNHG15 ameliorates ischemia/hypoxia-induced neuronal damage and microglial inflammation by regulating the miR-302a-3p/STAT1/NF-κB pathway.
研究领域:
神经科学
·
分子生物学
·
病理学
✓ 已验证
DOI
PubMed
高影响因子
Molecular Biomedicine
·
2025
·Vol. 6
·期 1
·1-18
·
IF 10.1
Zhang Shuqin,Cheng Yajia,Gao Yujia,Xu Feifei,Wang Yuna,Zhang Junling,Shang Yue,Li Deguan,Fan Saijun
With advancements in radiotherapy technologies, the detrimental effects of ionizing radiation on biological systems, particularly the hematopoietic system, have caused significant concern. N 6 -methyladenosine (m 6 A), the most pervasive representative of post-transcriptional modifications, plays critical roles in diverse biological events. Non-coding RNA comprises the vast majority of the human genome. This study aimed to explore the role of long non-coding RNA (lncRNA) m 6 A modification in γ-ray irradiation-induced hematopoietic injury. By using mouse models, it was found that γ-radiation rapidly damaged hematopoietic bone marrow cells (BMCs), triggering apoptosis, oxidative stress and DNA damage, along with up-regulation of m 6 A Reader proteins. We revealed the time-conditioned landscape of lncRNA m 6 A methylome of BMCs in the short term after radiation and found that a dynamic “change-then-recover” trend involved. LncRNA Snhg15 was identified as a key regulator through integration analysis of the methylome and transcriptome data. Its m 6 A modification was closely related to progression of radiation injury in BMCs. Further research demonstrated that the novel m 6 A Reader LRPPRC could interact with the modification site of Snhg15 , stabilize Snhg15 and promote its expression, thereby exacerbating radiation-induced injury to BMCs both in vitro and in vivo. Knockdown of Lrpprc or Snhg15 could alleviate the radiation injury to the hematopoietic system. Additionally, the LRPPRC- Snhg15 axis was involved in the radio-protective efficacy of gut microbiota-derived valeric acid. These findings uncover a novel mechanism by which m 6 A-modified lncRNA Snhg15 is stabilized by LRPPRC modulates γ-irradiation-induced hematopoietic injury, providing potential therapeutic targets for the prevention and treatment of radiation injuries.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）