MOLECULAR AND CELLULAR ENDOCRINOLOGY
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2023
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IF 4.1
Huimin Chen,Yue Liu,Tingwei Zhang,Tongtong Huang,Yating Lang,Qinghao Sheng,Yingxiao Liu,Zhijuan Kong,Ying Gao,Shangwei Lu,Meilin Yang,Xia Li,Rong Wang,Zhimei Lv
Podocyte dysfunction has been identified as a crucial pathological characteristic of diabetic nephropathy (DN). However, the regulatory effects of long non-coding RNAs (lncRNAs) in this process have not been fully elucidated. Here, we performed an unbiased RNA-sequencing (RNA-seq) analysis of renal tissues and identified a significantly upregulated long non-coding RNA, ENST00000585189.1 (lncRNA 585189), in patients with DN. Furthermore, lncRNA 585189 was positively correlated with renal insufficiency and was upregulated in both DN patients and high-glucose-induced human podocytes. Gain- and loss-of-function experiments revealed that silencing lncRNA 585189 decreased the production of ROS, rescued aberrant mitochondrial morphology and membrane potential, and alleviated podocyte damage caused by high glucose. Mechanistically, bioinformatics analysis predicted an interaction between lncRNA 585189 and hnRNP A1, which was subsequently confirmed by RIP, pull-down, and EMSA assays. Further investigation revealed that lncRNA 585189 destabilizes the hnRNP A1 protein, leading to the downregulation of its expression. Conversely, hnRNP A1 promoted the expression of lncRNA 585189. Moreover, both RIP and pull-down assays demonstrated a direct interaction between hnRNP A1 and SIRT1, which enhanced SIRT1 mRNA stability. Our findings suggest that lncRNA 585189 suppresses SIRT1 through hnRNP A1, thereby hindering the recovery from mitochondrial abnormalities and podocyte damage. In summary, targeting lncRNA 585189 is a promising strategy for reversing mitochondrial dysfunction and treating DN.
研究领域:
分子生物学
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肾病学
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糖尿病
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DOI
PubMed
高影响因子
Frontiers in Bioscience-Landmark
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2023
·Vol. 28
·期 7
·139
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IF 3.1
Yanan Zhang,Junjun Huang,Lingyan Yan,Rong Jia,Jihua Guo
Background: RUNX2 (Runt-related transcription factor 2) acts as a key regulator in the odontogenic differentiation of human dental pulp stem cells (hDPSCs). Moreover, the inclusion of exon 5 is important for RUNX2 function. Our previous study showed that Y-Box Binding Protein 1 (YBX1) promoted RUNX2 exon 5 inclusion and mineralization of hDPSCs. However, the regulatory mechanism of RUNX2 exon 5 alternative splicing needed further exploration. Methods: The expression level of heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) during the odontogenic differentiation of hDPSCs was analyzed by RT-PCR and Western blot. The roles of hnRNP A1 in the alternative splicing of RUNX2 exon 5 and the odontogenic differentiation of dental mesenchymal cells were analyzed by gain- and loss-of-function experiments. Results: Surprisingly, we found an alternative splicing factor, hnRNP A1, which had an opposite role to YBX1 in regulating RUNX2 exon 5 inclusion and odontogenic differentiation of hDPSCs. Through gain- and loss-of-function assay, we found that hnRNP A1 suppressed the inclusion of RUNX2 exon 5, resulting in the inhibition of odontoblastic differentiation. The overexpression of hnRNP A1 can inhibit the expression of ALP (alkaline phosphatase) and OCN (osteocalcin), and the formation of mineralized nodules during the odontogenic differentiation of both hDPSCs and mouse dental papilla cells (mDPCs), whereas the opposite results were obtained with an hnRNP A1 knockdown preparation. Conclusions: The present study indicated that hnRNP A1 suppressed RUNX2 exon 5 inclusion and reduced the odontogenic differentiation ability of hDPSCs and mDPCs.
研究领域:
分子生物学
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干细胞研究
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牙科学
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转录调控
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可变剪接
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DOI
PubMed
高影响因子
Nature Communications
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2026
·
IF 18.1
Zhijian Zhu,Rui Zhang,Haoran Kang,Meiyuan Chen,Hengjun Huang,Jing Wang,Ling Guo,Yuxing Li,Wenjing Chen,Limin Meng,Ruisi Wang,Ling Li,Kong-Peng Lam,Shengli Xu,Xijun Ou
Heterogeneous nuclear ribonucleoproteins (hnRNP) are key regulators of gene expression, yet the physiological functions of the highly homologous hnRNP A1 and A2B1 in B cells remain unclear. Here, we conditionally delete Hnrnpa1 and Hnrnpa2b1 in mouse B cells and find that loss of hnRNP A1 and A2B1 compromises the germinal center (GC) reaction during T cell-dependent immune responses. Loss of hnRNP A1 and A2B1 impairs GC B cell proliferation and high-affinity antibody production. Mechanistically, hnRNP A1/A2B1 bind UAG-rich motifs in Ezh2 pre-mRNA to promote Ezh2 exon 14 inclusion, thereby preserving EZH2 catalytic activity; in their absence, Ezh2 exon 14-skipping produces a catalytically inactive EZH2 isoform ( Ezh2 Δ14) with diminished repression of the cell cycle inhibitor Cdkn1a . The resulting CDKN1A accumulation restricts B cell proliferation, while Cdkn1a deletion partially rescues the GC defects in B cells deficient for hnRNP A1 and A2B1. Our findings thus uncover an hnRNP A1/A2B1–EZH2–CDKN1A axis that integrates RNA splicing with epigenetic regulation of B cell immunity. hnRNPs are RNA-binding proteins previously reported to regulate B cell differentiation and proliferation. Here, the authors show that hnRNP A1 and A2B1 support the germinal center reaction by retaining catalytically active EZH2, which reduces the cell cycle inhibitor CDKN1A, thereby promoting B cell proliferation.
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PubMed
高影响因子
Cell Death Discovery
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2025
·Vol. 11
·期 1
·542
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IF 7
Ji Kai,Zhou Leqi,Zhang Tianshuai,Fan Hao,Xie Gang,Man Wenjiang,Wang Can,Tian Yucheng,Chen Li,Wang Guimin,Liu Mulin,Zhu Bing,Zhang Wei,Yu Guanyu
Increasing evidence indicates that RNA-binding proteins and the reprogramming of lipid metabolism play crucial roles in tumorigenesis. However, the extent to which members of these families contribute, and whether targeting metabolic genes to affect overall protein production in cancer cells, remains largely unknown. This study analyzes CRC tissue samples and databases to reveal the high expression of hnRNP A1 in CRC and its critical role in tumorigenesis, proliferation, migration, and prognosis. Through combined sequencing analyses, we identified a novel mechanism by which PPARα regulates lipid metabolism. Our data indicate that hnRNP A1 is central to lipid metabolism reprogramming in CRC, promoting lipid accumulation by regulating PPARα mRNA stability, thereby influencing cell proliferation and apoptosis. Overall, hnRNP A1 could serve as a novel target for CRC therapy. Its involvement in cancer development offers new biological insights and potential therapeutic strategies. As a potential biomarker and therapeutic target, it presents novel approaches for the clinical management of CRC.
研究领域:
肿瘤学
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分子生物学
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癌症代谢
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RNA生物学
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细胞信号传导
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DOI
PubMed
高影响因子
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