CANCER LETTERS
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2023
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IF 9.7
Jiaoshun Chen,Haoxiang Zhang,Chaoyang Xiu,Chenggang Gao,Shihong Wu,Jianwei Bai,Qiang Shen,Tao Yin
In eukaryotes, N 6 -methyladenosine (m6A) is the most prevalent epigenetic alteration. Methyltransferase-like 3 (METTL3) is a key player in the control of m6A, although its function in pancreatic cancer is incompletely understood. In this study, we examined the role that METTL3 plays in pancreatic cancer cell proliferation and stemness. We discovered that in pancreatic cancer cells, METTL3-mediated m6A alterations regulate ID2 as a downstream target. The stability of ID2 mRNA was decreased and m6A modification was effectively eliminated by METTL3 knockdown in pancreatic cancer cells. We also demonstrate that m6a-YTHDF2 is necessary for the METTL3-mediated stabilization of ID2 mRNA. Additionally, we show that ID2 controls the stemness molecules NANOG and SOX2 via the PI3K-AKT pathway to support pancreatic cancer growth and stemness maintenance. Our data suggest that METTL3 may post-transcriptionally upregulate ID2 expression in an m6A-YTHDF2-dependent manner to further promote the stabilization of ID2 mRNA, which may be a new target for pancreatic cancer treatment.
研究领域:
癌症生物学
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分子生物学
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表观遗传学
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产品关联
DOI
PubMed
高影响因子
CELLULAR SIGNALLING
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2025
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IF 3.7
Xun Lu,Chengxin Ma,Dongxiao Li,Jianan Yang,Yuheng Sun,Bowen Liu,Binghai Zhao,Hongzhi Li
Hyperuricemia (HUA) is a prevalent metabolic disorder that contributes significantly to renal injury and may lead to the development of chronic kidney disease. Although previous studies have explored this condition, the molecular mechanisms underlying HUA-induced renal damage, particularly the role of small RNAs, remain inadequately understood. This study aimed to investigate the potential role of microRNA-93-5p (miR-93-5p) in HUA-associated renal injury. A comprehensive analysis was conducted to examine changes in miR-93-5p expression and its target gene, SMAD5, using knockout mouse models, cell cultures, transgenic techniques, and molecular biology methods. The findings demonstrated a significant upregulation of miR-93-5p in both HUA models and clinical serum samples, with a strong correlation to renal injury. Deletion of miR-93-5p resulted in increased SMAD5 expression and improved renal function, indicating that miR-93-5p contributed to renal injury by suppressing SMAD5 and promoting partial epithelial-mesenchymal transition in renal tubular epithelial cells. Transcriptomic analysis further revealed that miR-93-5p regulated numerous genes associated with inflammation, fibrosis, and apoptosis. Overall, these results underscore the pivotal role of miR-93-5p in HUA-induced renal damage through modulation of the SMAD5/Id2 signaling pathway, offering valuable insights into kidney disease pathophysiology and identifying potential therapeutic targets for clinical intervention.
研究领域:
分子生物学
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肾脏病学
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遗传学
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细胞生物学
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病理生理学
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产品关联
DOI
PubMed
高影响因子
Translational Oncology
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2026
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IF 4.9
Zhuo Chen,Meng-Lei Wang,Zhuo-Wen Zhang,Peng-Cheng Zhang,Qing-fang Yang,Yu-jing Weng,Jia-Long Shen,Wenxian Wang,Lan Shao
Background PD-1 blockade has become an important immunotherapeutic strategy, its clinical efficacy in non-small cell lung cancer (NSCLC) remains suboptimal. This study explores the effect and mechanism of sodium butyrate (NaB) and Clostridium butyricum ( C. butyricum ) combined with PD-1 inhibitors in NSCLC. Methods We established an NSCLC mouse model and evaluated tumor size, histopathology, apoptosis, cell proliferation, inflammatory factors, immune cell populations, and proteins of the HDAC1/ID2/IL-12R axis in the tumor, along with gut microbiome profiling. Results A combination of NaB or C. butyricum with PD-1 inhibitors significantly inhibited tumor growth and increased spleen and thymus indices. The combinations promoted tumor cell apoptosis, reduced the number of Ki67-positive proliferating cells, and increased IL-2, IL-6, IL-12, TNF-α, and IFN-γ levels in tumor tissues and serum. Additionally, the infiltration of CD4 + and CD8 + T cells in the tumor increased, while the Treg cells decreased. Importantly, the expressions of HDAC1 were markedly decreased, whereas ID2 and IL-12R levels increased in tumor tissues from NaB or C. butyricum with PD-1 inhibitor groups. Meanwhile, the combination of NaB or C. butyricum with PD‑1 inhibitors could alleviate the disturbance of gut microbiota by decreasing the Gordonibacter and increasing the WCHB1-32 . Significantly, the anti-CD8 antibody attenuated the inhibition of tumor growth conferred by NaB and PD‑1 inhibitors in vivo. Conclusions Collectively, NaB and C. butyricum enhanced the therapeutic action of PD‑1 inhibitors in murine models of NSCLC, possibly by modulating the HDAC1/ID2/IL-12R pathway, impacting intestinal microbiota and immune microenvironment.
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DOI
高影响因子
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