Communications Biology
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2025
·Vol. 8
·期 1
·1-15
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IF 5.1
Wu Lin,Zhang Fangyuan,Chen Huanhuan,Zhao Gang
Like-Smith protein 12 (LSM12), an RNA-binding protein, is highly expressed in tumor tissues of patients with lung squamous cell carcinoma (LUSC). However, the role of LSM12 in LUSC is unclear. In this study, overexpression of LSM12 promotes the proliferation, migration, and invasion and prevents the apoptosis of LUSC cells. In vivo, LSM12 accelerates the tumor growth and metastasis of LUSC cells using male BALB/c nude mice. Furthermore, we find that the Sterile alpha motif domain containing 4A (SAMD4A) is directly bound to the mRNA of LSM12 and accelerates the mRNA degradation. High-throughput omics analysis is performed to identify the potential target genes of LSM12 in LUSC cells. LSM12 regulates alternative splicing events and increases exon 13 skipped splicing of ARRB1 and mRNA expression. Our findings may provide fundamental research for the investigation of the development of LUSC and the potential role of LSM12 in LUSC cells.
研究领域:
肿瘤学
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分子生物学
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生物信息学
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PubMed
高影响因子
BMC Nephrology
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2025
·Vol. 26
·期 1
·1-14
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IF 2.4
Wang Yu,Zhang Jingjing,Tang Qian
Background Diabetic nephropathy (DN) is a primary contributor to end-stage renal disease, yet the underlying molecular mechanisms remain incompletely understood. This study aims to elucidate the role of RNA-binding proteins (RBPs) and RBP-alternative splicing (AS) regulatory networks in the pathogenesis of DN. Methods Two RNA-seq datasets (GSE117085 and GSE142025) were retrieved from the Sequence Read Archive (SRA) database. Regulated alternative splicing events (RASEs) and genes (RASGs) of RASEs, along with differentiated RBPs, were identified. Validated differentiated RBPs were correlated with clinical features using the Nephroseq v5 online platform. Using the DN mouse model and RT-qPCR, validated the alternative splicing of RNA. Results Our analysis revealed 15 differentiated RBP genes and 423 RASEs in the kidney cortex of DN rats compared to controls. Enrichment analysis highlighted lipid metabolism pathways for RASGs. Seven of the identified RBPs were validated in kidney biopsy samples from DN patients versus controls. A co-deregulatory network was constructed based on dysregulated RBPs and RASEs, with select RASGs identified. In vivo experiments, compared to normal mice, the mRNA levels of RPS19 were significantly elevated in the renal tissues of DN mice, while the levels of CPEB4 and CRYZ were markedly decreased. Conclusion In conclusion, this study provides evidence implicating dysregulated RBPs and RBP-AS regulatory networks in the development of diabetic nephropathy. The validated RBPs exhibited close associations with clinical biomarkers, reinforcing their potential as therapeutic targets for DN. These findings enhance our understanding of the molecular basis of DN and offer new insights for future research and intervention strategies. Clinical trial Not applicable.
研究领域:
分子生物学
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基因组学
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肾脏病学
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生物信息学
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发病机制
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PubMed
高影响因子
POULTRY SCIENCE
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2021
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IF 3.352
Zhenwu Huang,Song Jin,Zengpeng Lv
ABSTRACT Genistein is abundant in the soybean products, which exerts prominent effects on immune function. Little information is available about the effect of dietary genistein on thymic transcriptome, especially when suffering from lipopolysaccharide challenge. In this study, 180 one-day-old male broilers were randomly allocated to 3 groups: nonchallenged chicks given a basal diet ( CON ), and lipopolysaccharide-challenged chicks fed a basal diet ( LPS ), or lipopolysaccharide-challenged chicks fed a basal diet supplemented with 40 mg/kg genistein ( GEN ). Lipopolysaccharide injection induced thymocyte apoptosis and inflammatory reactions in the chicks. The results showed dietary genistein significantly reduced the percentage of CD3+ T lymphocytes by 10.04% and CD4+/CD8+ T lymphocyte ratio by 21.88% in the peripheral blood induced by lipopolysaccharide injection ( P < 0.05). In addition, genistein significantly reduced the thymus index by 50% and apoptotic index by 12.34% induced by LPS challenge ( P < 0.05). Transcriptomic analysis identified 1,926 DEGs (1,014 upregulated and 912 downregulated, P < 0.05) between GEN and LPS groups, which altered the mRNA expression profile and signaling pathways (Toll-like receptor, and NOD-like receptor signaling pathway) in the thymus. Furthermore, 5 splicing (AS) isoforms of the Drosophila Disabled-2 ( DAB2 ) gene were detected, which were significantly upregulated in the GEN group compared with that in the LPS group. In summary, dietary genistein supplementation altered the RNA expression profile and AS signatures in the thymus, and alleviated immune response against lipopolysaccharide challenge.
研究领域:
免疫学
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分子生物学
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营养学
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DOI
PubMed
高影响因子
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
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2024
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IF 4.2
Xiaoyi Huo,Yinna Wang,Zheming Liu,Jia Liu,Hang Zhu,Yong Zhou,Yilong Man,Xiaomao Zhou,Haihao Ma
The slowpoke channel responds to the intracellular calcium concentration and the depolarization of the cell membrane. It plays an important role in maintaining the resting potential and regulating the homeostasis of neurons, but it can also regulate circadian rhythm, sperm capacitation, ethanol tolerance, and other physiological processes in insects. This renders it a potentially useful target for the development of pest control strategies. There are relatively few studies on the slowpoke channels in lepidopteran pests, and their pharmacological properties are still unclear. So, in this study, the slowpoke gene of Plutella xylostella ( Pxslo ) was heterologous expressed in HEK293T cells, and the I-V curve of the slowpoke channel was measured by whole cell patch clamp recordings. Results showed that the slowpoke channel could be activated at −20 mV with 150 μM Ca 2+ . The subsequent comparison of the electrophysiological characteristics of the alternative splicing site E and G deletions showed that the deletion of the E site enhances the response of the slowpoke channel to depolarization, while the deletion of the G site weakens the response of the slowpoke channel to depolarization. Meanwhile, the nonspecific inhibitors TEA and 4-AP of the Kv channels, and four pesticides were tested and all showed an inhibition effect on the PxSlo channel at 10 or 100 μM, suggesting that these pesticides also target the slowpoke channel. This study enriches our understanding of the slowpoke channel in Lepidopteran insects and can aid in the development of relevant pest management strategies.
研究领域:
昆虫学
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药理学
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分子生物学
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害虫管理
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PubMed
高影响因子
Food & Function
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2024
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IF 5.1
Jingyi Ren,Jiarui Liu,Jinshi Zuo,Zhenao Zhang,Dan Huang,Xuanyi Liu,Miaomiao Lu,Yadong Zhang,Yang Su,Yuxia Ma
Background: Perfluorooctane sulfonate (PFOS) is a persistent, widely present environmental pollutant, and its toxicity to male reproduction has gradually attracted attention. Flaxseed oil (FO) is a dietary oil abundant in α-linolenic acid and has been demonstrated to possess multiple health benefits. However, whether FO protects against PFOS-induced testicular injury and its mechanism remain unclear. Methods: C57/BL6 mice were gavaged with different concentrations of FO or PFOS (10 mg kg−1) for 28 days. Blood and testicular tissues were collected for histopathology, proteomics, and biochemical and molecular analyses. Results: Our results showed that FO supplementation significantly attenuated PFOS-induced testicular injury, as indicated by histopathological changes, decreased oxidative stress level, increased sperm count, decreased rate of sperm malformation, and improved functional markers of spermatogenesis. Proteomic analysis showed that differentially expressed proteins were notably enriched in spliceosome pathways. Machine learning algorithms were used to screen the hub gene, and PRPF3 and PUF60 proteins were found to be important for FO to exert protective benefits to testicular injury. Western blot results confirmed that FO supplementation could increase the protein expression of PRPF3 and decrease the protein expression of PUF60 in PFOS-exposed mice. Conclusions: This study revealed that FO can alleviate PFOS-induced testicular dysfunction by regulating RNA alternative splicing. The spliceosome-related proteins PRPF3 and PUF60 may be the potential targets for FO to alleviate PFOS-induced testicular injury. FO supplementation may be an effective dietary intervention to prevent adverse effects of PFOS on testes.
研究领域:
毒理学
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生殖生物学
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营养科学
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分子生物学
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PubMed
高影响因子
Advanced Science
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2024
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IF 14.3
Weina Fan,Jian Huang,Fanglin Tian,Xin Hong,Kexin Zhu,Yuning Zhan,Xin Li,Xiangyu Wang,Xin Wang,Li Cai,Ying Xing
Alternative splicing (AS) generates protein diversity and is exploited by cancer cells to drive tumor progression and resistance to many cancer therapies, including chemotherapy. SNRPA is first identified as a spliceosome-related gene that potentially modulates resistance to platinum chemotherapy. Both the knockout or the knockdown of SNRPA via CRISPR/Cas9 and shRNA techniques can reverse the resistance of cisplatin-resistant lung adenocarcinoma (LUAD) cells to cisplatin. SNRPA overexpression enhanced the resistance of cisplatin-sensitive LUAD cells. Gene Ontology (GO) analysis reveals that SNRPA is associated with DNA damage repair. Depletion of SNRPA induced ERCC1 exon 8 skipping and reduced ERCC1–XPF complex formation, whereas SNRPA overexpression exerted the opposite effect. siRNAs targeting isoforms containing ERCC1 exon 8 [ERCC1-E8 (+)] reversed SNRPA-enhanced cisplatin resistance and DNA damage repair. Furthermore, the IGF2BP protein, an m 6 A reader, and the ELAVL1 protein, an RNA stabilizer recruited by IGF2BP1, are found to bind to the SNRPA mRNA. ELAVL1 promoted cisplatin resistance, DNA repair and ERCC1-E8 (+) expression in an SNRPA-dependent manner. In a mouse xenograft model, SNRPA- KO CRISPR enhanced the sensitivity of LUAD cells to cisplatin. Overall, this study illuminates the role of SNRPA in platinum-based drug resistance, thereby providing a novel avenue to potentially enhance chemosensitivity and improve the prognosis of patients with LUAD.
研究领域:
癌症生物学
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分子生物学
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遗传学
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药理学
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肿瘤学
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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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PubMed
高影响因子
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