ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2025
·
IF 6.1
Jingyu Wang,Xiaoli Guo,Yujiao Chen,Wei Zhang,Jing Ren,Ai Gao
Chronic benzene exposure causes hematotoxicity, yet the underlying molecular mechanisms remain incompletely understood. N6-methyladenosine (m6A) RNA modification has emerged as a critical regulator in various diseases, but its role in benzene-induced hematotoxicity is unclear. In this study, m6A mRNA microarray analysis revealed widespread alterations in m6A methylation following benzene exposure. Gene Ontology (GO) enrichment identified ubiquitin conjugating enzyme E2 G2 (UBE2G2) as a key m6A-methylated transcript associated with protein degradation pathways. Bioinformatics prediction and experimental validation (RIP-qPCR and MeRIP-qPCR) confirmed that the m6A reader YTHDF3 directly binds to UBE2G2 mRNA in an m6A-dependent manner. Benzene exposure downregulated YTHDF3 expression, leading to decreased UBE2G2 mRNA stability and expression. Overexpression of YTHDF3 reversed this suppression, confirming the regulatory relationship. Functionally, reduced UBE2G2 impaired ubiquitination of acyl-CoA synthetase long-chain family member 4 (ACSL4), resulting in its stabilization and upregulation, which promoted lipid peroxidation and ferroptosis. Notably, melatonin treatment ameliorated benzene-induced hematotoxicity by restoring the YTHDF3/UBE2G2/ACSL4 axis. In summary, this study identifies a novel epigenetic pathway—YTHDF3/m6A/UBE2G2/ACSL4—that mediates benzene-induced ferroptosis, and demonstrates the protective effect of melatonin through modulation of this axis.
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高影响因子
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
·
2019
·Vol. 393
·期 6
·951-966
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IF 2.058
Tong Rui,Zhang Jingru,Wang Chunyan,Li Qian,Wang Ling,Ju Mingxiu
Cervical cancer is the fourth most common female malignancy worldwide and microRNA (miR)-574-5p is a candidate oncogene in multiple cancers. The present study aimed to investigate the role and mechanism of miR-574-5p in cervical cancer. miR-574-5p inhibitors or mimics were transfected into cervical cancer cells to study the function of miR-574-5p. The effects of miR-574-5p on cell growth, invasion, and chemosensitivity were evaluated using CCK8, flow cytometry, transwell, immunofluorescence, and Western blotting analysis. Further depletion or forced expression of QKI was performed to explore the regulatory mechanism of miR-574-5p in cervical cancer. Up-regulation of miR-547-5p and down-regulation of QKI were observed in 30 cervical cancer tissues versus 30 adjacent normal tissues. Silencing of miR-574-5p increased apoptosis, inhibited proliferation, cell cycle progression, and cell invasiveness, as well as enhanced chemosensitivity towards cisplatin and doxorubicin in cervical cancer cells. Overexpression of miR-574-5p exerted promoting effect on cancer progression and metastasis. Knockdown of miR-574-5p induced an up-regulation of E-cadherin and down-regulation of cyclinD1, N-cadherin, matrix metallopeptidase 9 (MMP-9), and β-catenin in cervical cancer cells Moreover, QKI was verified as a target of miR-574-5p and involved in regulation of miR-574-5p-induced cervical cancer cell progression and metastasis. miR-574-5p functions to be oncogenic in cervical cancer, and its inhibition suppresses cervical cancer progression and metastasis as well as enhances chemosensitivity by targeting QKI. Therefore, miR-574-5p is suggested as a potential therapeutic target for cervical cancer treatment.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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高影响因子
Science Signaling
·
2026
·Vol. 19
·期 948
·
IF 7
Qian Zhang,Yuedan Zhu,Yi Chen,Wenhao Hou,Aolong Sun,La Yan,Xingzhu Liu,Yu Yuan,Chaoxin Gao,Junfeng Xie,Rui Zhang,Haiyang Chen
Aging impairs intestinal stem cell (ISC) function, disrupting epithelial homeostasis and regenerative repair. Loss of ISC quiescence promotes intestinal dysfunction and contributes to organismal aging. Here, we report an epitranscriptomic mechanism through which a decrease in adenosine-to-inosine (A-to-I) RNA editing by the adenosine deaminase ADAR in ISCs during aging disrupts a conserved signaling axis that maintains ISC quiescence. In Drosophila melanogaster , ISC-specific loss of dADAR triggered hyperproliferation and tissue aging, whereas dADAR overexpression reduced age-related gut dysfunction and extended life span. Intestinal injury induced a decrease in dADAR, which was necessary for tissue regeneration, and in the zinc finger protein dZn72D, which stabilized dADAR to support intestinal homeostasis during aging. dADAR edited transcripts encoding the RNA binding protein Pumilio (dPUM) to generate an isoform that inhibited translation of two components of the mitogen-activated protein kinase (MAPK), dEGFR and dERK, thereby maintaining ISC quiescence. The abundance of ADAR2 and of the dZn72D ortholog ZFR decreased in human colonic crypts with aging and in mouse colon after injury, suggesting that attenuation of ADAR activity may play a conserved role in ISC aging and in facilitating colonic regeneration. Our work identifies a conserved mechanism of epitranscriptomic regulation that safeguards tissues and the decay of ADAR-mediated RNA editing as a form of age-related epigenetic information loss that disrupts ISC homeostasis.
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PHYTOMEDICINE
·
2025
·
IF 8.3
XiaoMing Zhou,ChenXi Zhang,Wen Shen,RuiFei Zhuang,ShenLin Liu,JinDi Liu
Background Curzerene, a bioactive compound from Curcuma zedoaria, exhibits anticancer effects, but its role in gastric precancerous lesions remains poorly understood. This study investigates the potential of Curzerene in inhibiting gastric precancerous lesions progression by regulating the long non-coding RNA (LncRNA) AFAP1-AS1 and the Hippo/YAP signaling pathway. Methods In vitro, a gastric precancerous cell model (MC cells) was established by treating GES-1 cells with MNNG. The effects of Curzerene on cell proliferation, migration, and EMT were assessed using CCK-8, scratch assays, RT-PCR, and Western blot. In vivo, a gastric precancerous mouse model was induced by MNU, and the therapeutic effects of Curzerene (14 mg/kg and 28 mg/kg) were evaluated through histological and molecular analysis. Results Curzerene treatment significantly inhibited MC cell proliferation, migration, and EMT, downregulating LncRNA AFAP1-AS1 and YAP while upregulating E-cadherin and downregulating N-cadherin. In vivo, Curzerene alleviated gastric mucosal damage, reduced cancer markers (P53 and CD133), and improved histopathology. Transcriptomic analysis identified the Hippo/YAP pathway as a key mediator of Curzerene’s effects. YAP activation reversed Curzerene’s inhibitory effects on EMT, confirming the involvement of this pathway. Conclusion Curzerene effectively inhibits gastric precancerous lesion progression by targeting the YAP signaling and the following LncRNA AFAP1-AS1 to suppress EMT. These findings suggest Curzerene’s novel potential as a promising therapeutic agent for early intervention and prevention of gastric cancer.
研究领域:
肿瘤学
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分子生物学
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药理学
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高影响因子
JOURNAL OF BIOMATERIALS APPLICATIONS
·
2024
·
IF 2.3
Guojie Lu,Huiling Zhong,Jianwei Gao,Yaosen Zhang
The long non-coding RNA HOTAIR and the Hedgehog-Gli1 signaling pathway are closely associated with tumor occurrence and drug resistance in various cancers. However, their specific roles in the development of EGFR-TKIs resistance in non-small cell carcinoma remain unclear. To address the issue of EGFR-TKIs resistance, this study utilized the electrospray method to prepare sodium alginate microspheres encapsulating HOTAIR siRNA (SA/HOTAIR siRNA) and investigated its effects on RNA interference (RNAi) in the gefitinib-resistant cell line PC9/GR. Furthermore, the study explored whether HOTAIR could modulate EGFR-TKIs resistance through the Hedgehog-GLi1 signaling pathway. The experimental results showed that sodium alginate (SA) microspheres demonstrated excellent biocompatibility with high encapsulation efficiency and drug-loading capacity, effectively enhancing the silencing efficiency of siRNA. HOTAIR siRNA significantly inhibited the proliferation, migration, and invasion abilities of PC9/GR cells while promoting apoptosis. Additionally, HOTAIR siRNA effectively suppressed tumor growth and downregulated the Hedgehog-GLi1 pathway and anti-apoptotic proteins, which were confirmed in animal experiments. Moreover, SA/HOTAIR siRNA exhibited superior inhibition of cellular and tumor functions compared to using HOTAIR siRNA alone. Clinical research findings indicated that monitoring the expression level of HOTAIR in the serum and urine samples of NSCLC patients before and after receiving EGFR-TKIs treatment can predict the efficacy of EGFR-TKIs to a certain extent. This study provided evidence that HOTAIR siRNA effectively mitigated the development of acquired resistance to EGFR-TKIs by inhibiting the Hedgehog-GLi1 pathway. Furthermore, it introduced a reliable and long-lasting drug delivery system for combating acquired resistance to EGFR-TKIs.
研究领域:
肿瘤学
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分子生物学
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药学
·
癌症治疗
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PubMed
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2021
·Vol. 25
·期 8
·3744-3753
·
IF 5.31
Zhong-Sheng Xiao,Lei Zhao,Xiao-Ning Zhang,Han-Xian Li,Zhi-Hui Yin
It has been reported that rs67085638 in long non-coding RNAs (lncRNA)-CCAT1 was associated with the risk of tumorigenesis. Also, CCAT1 could affect chemoresistance of cancer cells to paclitaxel (PTX) via regulating miR-24-3p and FSCN1 expression. In this study, we aimed to investigate the effect of rs67085638 on the expression of CCAT1/miR-24-3p/FSCN1 and the response of colon cancer to the treatment of PTX. 48 colon cancer patients were recruited and grouped by their genotypes of rs67085638 polymorphism as a CC group (N = 28) and a CT group (N = 20). PCR analysis, IHC assay and Western blot, TUNEL assay and flow cytometry were conducted. LncRNA-CCAT1 and FSCN1 mRNA/protein were overexpressed, whereas miR-24-3p was down-regulated in the CT-genotyped patients and cells compared with those in the CC-genotyped patients and cells. The survival of colon cancer cells was decreased, whereas the apoptosis of colon cancer cells was increased by PTX treatment in a dose-dependent manner. MiR-24-3p was validated to target lncRNA-CCAT1 and FSCN1 mRNA, and the overexpression of CCAT1 could reduce the expression of miR-24-3p although elevating the expression of FSCN1. Knockdown of lncRNA-CCAT1 partly reversed the suppressed growth of CT-genotyped tumours. And the knockdown of lncRNA-CCAT1 partly reversed the dysregulation of lncRNA-CCAT1 and FSCN1 mRNA/protein in rs67085638-CT + NC shRNA mice. The findings of this study demonstrated that the presence of the minor allele of rs67085638 increased the expression of CCAT1 and accordingly enhanced the resistance to PTX. Down-regulation of CCAT1 significantly re-stored the sensitivity to PTX of colon cancer cells.
研究领域:
癌症生物学
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分子生物学
·
遗传学
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PubMed
高影响因子
Aging-US
·
2019
·
IF 5.515
Chen Diling,Guo Yinrui,Qi Longkai,Tang Xiaocui,Liu Yadi,Yang Xin,Hu Guoyan,Shuai Ou,Yong Tianqiao,Wang Dongdong,Xie Yizhen,Burton B. Yang,Wu Qingping
Recent studies have demonstrated circular RNAs (circRNAs) to be widely expressed and to have important physiological functions. However, the expression, regulation, and function of circRNAs in neuroglial cells are unknown. Herein, we characterized the expression, regulation, and function of circRNAs in astrocytes. Astrocyte circRNAs were identified by computational analysis of newborn SD rat primary astrocytes cultured with 20 g/L D-galactose. In this manner, 7376 circRNAs were identified, among which most circRNAs (5754) were derived from annot_exons, whereas 27 were antisense, 853 were exon/intron, 329 were intergenic, 41 were intronic, and 372 were one exon. Among these, circNF1-419 was demonstrated to regulate autophagy, in over-expressing circNF1-419 transfected astrocytes, through the PI3K-I/Akt-AMPK-mTOR and PI3K-I/Akt-mTOR signaling pathways. An adenovirus associated virus packaging system (virus titer 1 ×10 12 ), over-expressing circNF1-419 and injected into mouse cerebral cortex, showed autophagy enhancing activity by binding the proteins Dynamin-1 and Adaptor protein 2 B1 (AP2B1). This binding regulated aging markers (p21, p35/25, and p16) and inflammatory factors (TNF-α and NF-κB), and reduced the expression of Alzheimer’s disease marker proteins (Tau, p-Tau, Aβ 1-42 , and APOE), which delayed senile dementia. Transcriptome analysis of the brain showed that circNF1-419 improved other signaling pathways, especially those related to the synapses of SAMP8 mice. These findings provide novel insights into circNF1-419 and its potential usefulness for the diagnosis and treatment of dementia by regulating Dynamin-1 and AP2B1 mediated autophagy.
研究领域:
神经科学
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分子生物学
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细胞生物学
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衰老研究
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神经退行性疾病
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高影响因子
DIGESTIVE AND LIVER DISEASE
·
2021
·
IF 4.088
Si-Biao Su,Lin Tao,Xiao-Le Liang,Wen Chen
Background Liver fibrosis is a common disease that can lead to hepatic failure. Aims Our aims were to reveal the role of GAS5 in the regulation of liver fibrosis. Methods LX-2 human hepatic satellite cells (HSCs) were cultured and activated using TGF-β1 treatment. A CCK-8 assay was performed to assess cell viability. A luciferase assay was employed to monitor the interactions between miR-433–3p and GAS5 or toll-like receptor 10 (TLR10). Western blotting and real-time quantitative PCR (RT-qPCR) were applied to detect the expression levels of α-SMA, Col. I, PCNA-, MMP2-, MMP9-, TLR10-, and NF-κB-related molecules at the protein and RNA levels. Results GAS5 and TLR10 were decreased while miR-433–3p was upregulated in TGF-β1-activated LX-2 cells. Upregulation of GAS5 or downregulation of miR-433–3p suppressed HSC activation, and luciferase assays indicated that miR-433–3p binds with GAS5 and the 3′-UTR of TLR10. MiR-433–3p upregulation and TLR10 downregulation rescued the impacts of GAS5 overexpression or miR-433–3p knockdown on LX-2 cells. Upregulation of GAS5 also suppressed the phosphorylation of NF-κB through the miR-433–3p/TLR10 axis. Conclusion LncRNA GAS5 exerts an inhibitory effect on HSC activation by suppressing NF-κB signalling through regulation of the miR-433–3p/TLR10 axis.
研究领域:
分子生物学
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细胞生物学
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医学遗传学
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PubMed
高影响因子
Evidence-based Complementary and Alternative Medicine
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2023
·
IF 2.65
Hui Wang,HaiTang Ren
The action mechanism in which circular RNA (circ) SMARCA5 targeted nasopharyngeal carcinoma (NPC) cell proliferation, migration, invasion, and apoptosis via microRNA (miR)-582-3p/phosphatase and tensin homolog (PTEN) axis was explored. The examination was performed via reverse transcription-quantitative polymerase chain reaction (RT-qPCR), discovering that circSMARCA5 was elevated while miR-582-3p was silenced in NPC tissues and cells. E-cadherin and N-cadherin were detected. The results illustrated transfection with si-circSMARCA5 or miR-582-3p-mimic was available to repress cancer cell advancement, and E-cadherin was augmented. Transfection with pcDNA 3.1-circSMARCA5 or miR-582-3p-inhibitor was available to accelerate cancer cell advancement, and N-cadherin was augmented. MiR-582-3p-inhibitor blocked the suppression of si-circSMARCA5 on NPC. The si-PTEN blocked the malignant behavior of pcDNA 3.1-circSMARCA5 against NPC. The binding sites between circSMARCA5 and miR-582-3p and between miR-582-3p and PTEN were verified. Linear analysis results illuminated the expression pattern of circSMARCA5 was opposite to miR-582-3p, while the expression pattern of circSMARCA5 was positively associated with PTEN. In brief, the results of the research clarified circSMARCA5 modulated NPC cells’ vital movement via the miR-582-3p/PTEN molecular axis.
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PATHOLOGY RESEARCH AND PRACTICE
·
2021
·
IF 3.25
Yang Yang,Guoying Zhang,Jian Li,Rui Gong,Yingbao Wang,Yang Qin,Qinrong Ping,Libing Hu
Background Increasing evidences have proved that long noncoding RNAs (lncRNAs) regulate the occurrence of bladder cancer (BC) and participate in various pathophysiology processes. However, little is unknown about the role of lncRNAs in drug resistance of BC cells. In this study, we explored the role of non-coding RNA activated by DNA damage (NORAD) in the gemcitabine (GEM) resistant of BC cells and explored its potential mechanism. Methods Real-time quantitative PCR (RT-qPCR) was used to detect the expression of NORAD and miR-155–5p of BC cells. Cell counting kit-8 (CCK-8) and Western blot were used to detect cell inhibition rate and the expression of WEE1 G2 checkpoint kinase (WEE1), P-glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP1). Flow cytometry detected cell cycle and apoptosis . Dual luciferase reporter gene assay and RNA immunoprecipitation (RIP) assay were used to confirm the targeting relationship between miR-155–5p, NORAD and WEE1. The xenograft model was used to observe the function of NORAD in vivo. immunohistochemistry (IHC) assay was used to detect the expression of WEE1, caspase-3 and Ki67 in tumor tissues. Results NORAD highly expressed in GEM-resistant BC cell lines . Knockdown of NORAD significantly inhibited the proliferation of T24/GEM cells, the expression of drug-resistant proteins P-gp and MRP1, inhibit the G0/G1 phase of cells, and induce cell apoptosis. Knockdown of NORAD reversed the promotion effect of miR-155–5p on WEE1 expression and promoted the sensitivity of T24/GEM cells to GEM. In vivo , knockdown of NORAD inhibited the tumor growth, and enhanced the GEM-sensitivity in mice. Conclusion These data highlight the potential of NORAD acts as a therapeutic target for BC GEM resistance. It revealed the vital roles of NORAD/miR-155–5p/WEE1 axis in GEM resistant BC cells, providing a novel therapeutic strategy for BC.
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Analytical Methods
·
2020
·Vol. 12
·期 48
·5833-5838
·
IF 2.596
Zheng Yuan,Peng Xu,Fangzhi Yu,Dapeng Zhang,Qiang Zhao,Wenqiang Yu,Hailin Wang
Affinity Capillary Electrophoresis (ACE) is a useful analytical tool to study noncovalent interactions. However, it remains challenging for ACE to measure weak and unstable interactions due to the fast dissociation of the binding complex and the possible destruction of the complex by a high electric field. In this study, we proposed a two-direction migration strategy that enables ACE to detect weak and unstable but important interactions by decreasing the migration distance of the binding complex and controlling the opposite migration direction of the free probe. By synthesizing a polyacrylamide-coated neutral capillary, free of electroosmotic flow, two-direction CE migration of basic peptides (positively charged) and peptide–RNA complexes (negatively charged) was achieved. Furthermore, the weak interactions between small nuclear U2 RNA and histone peptides were detected by this two-direction migration CE approach. The effects of the methylation states of histone peptides on the weak peptide–RNA interactions were also explored by this new approach. Collectively, the suggested modification of the ACE method is able to qualitatively characterize weak interactions.
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2023
·
IF 6.8
Zhi Qu,Limin Liu,Xiaoliang Wu,Peisen Guo,Zengli Yu,Peixi Wang,Yuzhen Song,Shanqing Zheng,Nan Liu
Accumulation of the heavy metal Cadmium (Cd) in the ovaries and placenta can affect the structure and function of these organs and induce female reproductive toxicity. This toxicity may be due to Cd’s similarity to estrogen and its ability to disrupt endocrine systems. However, the exact molecular mechanism by which Cd causes reproductive toxicity at the transcriptome level remains poorly understood. Hence, this study aimed to observe Cd-induced reproductive damage at the gene level, scrutinize the repercussions of Cd exposure on oogenesis, and explicate the putative pathogenesis of Cd-induced oogenesis based on Caenorhabditis elegans ( C. elegans ) as an in vivo model. The results showed that Cd exposure significantly decreased the number of offspring and prolonged the reproductive span of C. elegans . Cd exposure also reduced the number of cells in mitosis and the pachytene and diakinesis stages of meiosis, thereby disrupting oogenesis. Combined with transcriptional sequencing and bioinformatics analysis, a total of 3167 DEmRNAs were identified. Regarding gene expression, cul-6 , mum-2 , and vang-1 were found to be related to Cd-induced reproductive toxicity, and their competing endogenous RNA networks were constructed. We observed that mutations of mom-2 and vang-1 in the Wnt pathway could induce susceptibility to Cd-caused meiosis injury. In conclusion, the results indicated that Cd could impair the oogenesis of C. elegans and the Wnt pathway might serve as a protective mechanism against Cd reproductive toxicity. These findings contribute to a better understanding of the damaging effects and molecular biological mechanisms of Cd on the human reproductive system.
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