Synthetic and Systems Biotechnology
·
2025
·
IF 4.4
Yixin Sun,Qi Sun,Tiantian Gao,Shumin Ren,Xiaomei Hu
Efficient cellulase production is essential for its application in green bioprocessing, yet the transcriptional regulation of cellulase biosynthesis in Talaromyces sp. remains largely uncharacterized. In this study, we elucidate the regulatory functions of TeXlnR and TeAmyR in Talaromyces endophyticus . Our results demonstrate that TeXlnR, as a potent transcriptional activator, enhances enzyme production by over 33 %. RNA-seq analysis shows that TeXlnR overexpression upregulates 33 cellulase genes and 11 hemicellulase genes, while concurrently repressing the expression of the transcription factor TeAmyR . Further investigation identified TeAmyR as a repressor of cellulase production in T. endophyticus . EMSA and yeast one-hybrid analyses confirmed the specific competitive binding of these two transcription factors to the promoter regions of cellulase genes eg5B and eg12A . TeXlnR both directly activates target gene transcription and indirectly promotes cellulase synthesis by downregulating TeAmyR expression to reduce its competitive binding to promoters. These findings provide direct evidence for competitive regulation by transcription factors in Talaromyces sp. and establish a theoretical foundation for the rational engineering of industrial strains with improved cellulase production.
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Cell Reports Medicine
·
2024
·
IF 11.7
Chengyu Li,Xin Shao,Shujing Zhang,Yingchao Wang,Kaiyu Jin,Penghui Yang,Xiaoyan Lu,Xiaohui Fan,Yi Wang
Cells respond divergently to drugs due to the heterogeneity among cell populations. Thus, it is crucial to identify drug-responsive cell populations in order to accurately elucidate the mechanism of drug action, which is still a great challenge. Here, we address this problem with scRank, which employs a target-perturbed gene regulatory network to rank drug-responsive cell populations via in silico drug perturbations using untreated single-cell transcriptomic data. We benchmark scRank on simulated and real datasets, which shows the superior performance of scRank over existing methods. When applied to medulloblastoma and major depressive disorder datasets, scRank identifies drug-responsive cell types that are consistent with the literature. Moreover, scRank accurately uncovers the macrophage subpopulation responsive to tanshinone IIA and its potential targets in myocardial infarction, with experimental validation. In conclusion, scRank enables the inference of drug-responsive cell types using untreated single-cell data, thus providing insights into the cellular-level impacts of therapeutic interventions.
研究领域:
生物信息学
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系统生物学
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医学
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SENSORS AND ACTUATORS B-CHEMICAL
·
2021
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IF 7.46
Xingjie Wu,Hong Yang,Wei Li,Ling Tao,Qingteng Wang,Yingzu Jin,Xuecheng Sun,Xiangchun Shen
The prompt diagnosis of acute myocardial infarction (AMI) for patients with acute ischemic-type chest pain is critical for timely AMI treatment and lowering its casualty rate. In this article, we developed a multiparametric detection technique for AMI related microRNAs (miRNAs), which is based on the polymerization induced fluorescence-off (PIFO) signal amplification technique. PIFO can be implemented on a specially designed microfluidic chip equipping a fluorescence sensor, which is able to profile 3 miRNAs simultaneously in 45 min with a detection limit of 6100 miRNAs copies. Comparing with other polymerization-based signal amplification techniques, PIFO is rapid, oxygen-independent, multiparametric, and can be performed in ambient environment. The miniaturized PIFO device can be further applied to analyze AMI related miRNAs in clinical serum samples, and displays excellent performance in distinguishing AMI patients from patients with other cardiovascular diseases. Moreover, PIFO shows a high accuracy for AMI diagnosis among patients with low hypersensitivity troponin I level (< 0.1 ng mL −1 ) as a result of the early and fast respond to AMI onset by miRNAs.
研究领域:
医学诊断
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分子生物学
·
生物传感器
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Journal of Translational Medicine
·
2024
·Vol. 22
·期 1
·1-19
·
IF 6.1
Xu Haotian,Zheng Yue,Wu Jiaxi,Zhang Ruirui,Zhao Qingyun,Chen Sixian,Peng Wenyi,Cai Dunyu,Gao Yihong,Chen Xingcai,Li Deqing,yuan Shengyi,Li Gang,Nan Aruo
Lung cancer is the primary cause of cancer-related death worldwide, and its global incidence and mortality rates remain high. The differential expression of circular RNAs (circRNAs) can affect the development of cancer, but the mechanisms by which circRNAs regulate lung cancer progression remain unclear. In this study, we identified circSORBS1, a circRNA that has not been previously described in lung cancer and is significantly underexpressed in lung cancer tissues, blood and cell lines, and the low expression of circSORBS1 correlated with tumour grade and prognosis. In vitro and in vivo functional experiments revealed that circSORBS1 overexpression inhibited cell proliferation and migration while enhancing apoptosis. Mechanistically, circSORBS1 acts as a sponge for miR-6779-5p, indirectly inhibiting RUFY3 mRNA degradation. Simultaneously, it binds to RUFY3 mRNA to enhance its stability. This dual regulatory mechanism leads to an increase in RUFY3 protein levels, which ultimately activates the YWHAE/BAD/BCL2 apoptotic signalling pathway and suppresses lung cancer progression. Our findings not only increase the knowledge about the regulatory pattern of circRNA expression but also provide new insights into the mechanisms by which circRNAs regulate lung cancer development.
研究领域:
肿瘤学
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分子生物学
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癌症生物学
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基因组学
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JOURNAL OF SEPARATION SCIENCE
·
2021
·Vol. 44
·期 17
·3208-3218
·
IF 3.645
Yichao Qin,Qisheng Zhong,Ying Zhang,Xiuying Lin,Pengcheng Fu,Huan Lin
Post-transcriptional modification of nucleosides is observed in almost all elements of RNA. Modified nucleosides finely tune the structure of RNA molecules and affect vital functions, such as the modified wobble position 34 of transfer RNAs expanding the reading preference of anticodons to codons. Recent investigations have revealed that the modification species and their frequencies in an RNA element are not stable but vary with specific cellular factors including metabolites and particular proteins (writers, readers, and erasers). To understand the link between dynamic RNA modifications and biological processes, sensitive and reliable methods for determining modified nucleosides are required. In this study, micro-flow (8 μL/min) hydrophilic interaction liquid chromatography was coupled with triple quadrupole mass spectrometry for the simultaneous determination of adenosine, uridine, cytidine, guanosine, and 20 modified nucleosides. The method was calibrated using 0.1–1000 nM standards (∼0.03–300 ng/mL) and successfully applied to the determination of transfer RNA modifications in the model cyanobacterium Synechococcus elongatus PCC 7942. A protocol for the isolation of a clean transfer RNA pool was optimized, requiring only 25 ng for the identification and quantification of transfer RNA modifications. This micro-flow liquid chromatography-tandem mass spectrometry method constitutes the first step toward monitoring dynamic ribonucleoside modifications in a limited RNA sample.
研究领域:
分析化学
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分子生物学
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生物化学
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微生物学
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Bioengineered
·
2021
·
IF 3.269
Jing Wang,Yan Liu,Hongbing Cai,Hong Jiang,Wei Li,Yuying Shi
Cervical cancer (CC) is one of the most common malignancies among women. It has been demonstrated that long coding RNAs (lncRNAs) play a crucial role in CC. The purpose of this study was to investigate the role of the colon cancer associated transcript 2 (CCAT2) lncRNA in CC and elucidate its possible mechanisms of action. The expression of CCAT2, the miR-493-5p microRNA (miRNA), and mRNA was detected using qRT-PCR. Cell viability, proliferation, and migration and invasion were determined using the MTT, colony formation, and transwell assays, respectively. The interactions between miR-493-5p and CCAT2 or cAMP response element-binding protein 1 (CREB1) were verified using the luciferase and RNA pull-down assays. The effects of CCAT2 knockdown on in vivo tumor growth were determined using tumor xenografts and immunohistochemistry assays. The expression of CCAT2 was upregulated in CC cells and tissues. However, the knockdown of CCAT2 inhibited the proliferation and epithelial-mesenchymal transition (EMT) of CC cells in vitro and suppressed tumor growth in vivo. Mechanistically, CCAT2 functions as a competing endogenous RNA (ceRNA) to upregulate the expression of CREB1 by binding to miR-493-5p. The overexpression of CREB1 or downregulation of miR-493-5p antagonized the effect of CCAT2 knockdown on the proliferation and EMT of CC cells. The knockdown of CCAT2 suppressed the aggressiveness of CC via the miR-493-5p/CREB1 axis. Therefore, CCAT2 is likely to be a promising therapeutic target for CC.
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
ARCHIVES OF INSECT BIOCHEMISTRY AND PHYSIOLOGY
·
2026
·Vol. 121
·期 2
·e70137
·
IF 2
Bin Li,Dao-Shuang Zhu,Yong-Hui Zhang,Chuan-Tao Xu,De-Xin Chen,Mao-Ye Li,Su Liu
In insects, cytochrome P450 monooxygenases (CYPs) play a pivotal role in the detoxification of various insecticides. The cigarette beetle, Lasioderma serricorne , is an economically important pest of stored products, for which pyrethroid insecticides are increasingly used. Nevertheless, the responses and functions of CYPs in L. serricorne under pyrethroid exposure remain poorly understood. In this study, three full-length CYP cDNAs were identified from L. serricorne and designated as CYP6BK29 , CYP6SY1 , and CYP6TE1 . Phylogenetic analysis revealed that these CYPs belong to the CYP3 clan and the CYP6 family. Reverse transcription–quantitative PCR showed that CYP6BK29 and CYP6SY1 were predominantly expressed in the larval midgut, whereas CYP6TE1 transcripts were enriched in the fat body. The expression of CYP6BK29 peaked in the third- and fourth-instar larvae, while CYP6SY1 was specifically highest in the fourth-instar. In contrast, CYP6TE1 showed the highest mRNA levels in adults. Exposure to a sublethal dose (LD 30 ) of lambda-cyhalothrin (LCT) significantly upregulated the mRNA levels of CYP6BK29 and CYP6TE1 , but not that of CYP6SY1 . RNAi-mediated knockdown of CYP6BK29 significantly increased the susceptibility of larvae to LCT. In contrast, silencing CYP6SY1 or CYP6TE1 had no significant effect on larval survival under LCT exposure. These results provide evidence that CYP6BK29 contributes to LCT detoxification in L. serricorne , highlighting its potential as a molecular target for novel pest management strategies. Summary Characterization of three novel CYP genes ( CYP6BK29 , CYP6SY1 , and CYP6TE1 ) in Lasioderma serricorne . Successful transcriptional knockdown of all three genes via RNAi. CYP6BK29 knockdown enhances larval susceptibility to lambda-cyhalothrin, implicating its role in detoxification.
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Plant Nano Biology
·
2026
·
IF 9.1
Zhiwen Wang,Mengru Shi,Ye Sun,Qinghua Zhang,Bingyin Zhang,Yang Zheng,Zhaolin Xue,Xili Liu
Gray mold is a fungal disease that affects many crops, including tomatoes, and causes massive economic losses worldwide. A novel control system is urgently needed because of the fungus’s high genetic variability and resistance to multiple fungicides. Spray-induced gene silencing is an effective way to control plant pests by triggering RNA interference (RNAi) and blocking key genes in them. However, directly silencing susceptibility genes in plants to control disease remains to be studied. This approach could be a more efficient way to induce RNAi than targeting the pest’s genes. Here, three disease susceptibility genes of tomato were efficiently targeted by RNA based nano fungicides coupled with double-stranded RNA-carbon quantum dots (dsRNA-CDs). The novel RNA based nano fungicides offered an excellent effect on dsRNA preservation and cellular delivery, also facilitated the production of jasmonic acid in plants, which enabled these fungicides with good inhibitory effects on gray mold, indicating that they could be a promising way to control this notorious disease. Moreover, the fungicides specifically silenced the target genes and had no side effects on plants. Therefore, the novel RNA based nano fungicides could be efficient tools to control gray mold in tomatoes, and the plant susceptibility gene-based system is a potential way to control various plant diseases.
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ONCOLOGY REPORTS
·
2025
·Vol. 54
·期 1
·1-16
·
IF 3.9
Yubo Yan,Xianglong Kong,Xiangyuan Jin,Jianlong Bu,Boxiong Ni,Zuqin Rao,Junnan Guo,Shidong Xu
Ring finger protein 125 (RNF125), a ubiquitin E3 ligase, has been reported to act as a tumor suppressor in several cancers, but its precise function in lung adenocarcinoma (LUAD) has not been elucidated. In the present study, through bioinformatics analysis and immunohistochemistry in LUAD and non‑cancerous samples, it was demonstrated that RNF125 was significantly downregulated in lung cancer. Low levels of RNF125 expression were associated with metastatic status, advanced tumor stage and poor overall survival in LUAD. The results of gain‑ and loss‑of‑function experiments demonstrated that RNF125 inhibited proliferation, colony formation, migration and invasion of LUAD cells. In addition, RNF125 increased the sensitivity of LUAD cells to cisplatin. Mechanistically, RNF125 interacted with programmed cell death ligand 1 (PD‑L1) and reduced PD‑L1 expression levels in LUAD cells. Furthermore, IL‑2 secretion by Jurkat T cells was significantly suppressed when co‑cultured with RNF125‑silenced LUAD cells. NK‑92 cell lysis of RNF125‑silenced LUAD cells was also weaker compared with that of control LUAD cells, suggesting that RNF125 knockdown enhanced the immune evasion ability of LUAD cells. Notably, the results of the present study identified that the RNA‑binding protein muscleblind‑like 1 (MBNL1) is the upstream regulator of RNF125 in LUAD. MBNL1 increased the stability of the RNF125 transcript in LUAD cells and knockdown of RNF125 reversed the antitumor effect of MBNL1 on LUAD cells. In conclusion, the present study demonstrated the tumor suppressor role of RNF125 in LUAD and implicated MBNL1 as an upstream regulator of RNF125 in LUAD. These findings contributed to an improved understanding of the molecular features of LUAD progression.
研究领域:
肿瘤学
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分子生物学
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免疫学
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2025
·
IF 6.1
Sili Chen,Xiangyu Ding,Tao Zheng,Hao Deng,Qiaoyuan Yang
Benzo[ghi]perylene (BghiP), a prevalent high-molecular-weight (HMW) polycyclic aromatic hydrocarbon (PAH) with significant environmental exposure, poses potential health risks that remain inadequately characterized. This study investigated the respiratory toxicity of BghiP exposure and its underlying mechanisms in vitro (human bronchial epithelial cells BEAS-2B and 16HBE) and in vivo (mouse model). Chronic exposure to environmentally relevant concentrations of BghiP (500 ng/mL for 2 weeks in vitro ; 500 µg/m 3 for 4 weeks in vivo ) significantly reduced cell proliferation, induced apoptosis and cell cycle arrest, and caused DNA damage in BEAS-2B and 16HBE cells. In vivo, BghiP exposure increased lung coefficients, induced pathological alterations, and triggered pulmonary inflammation. Mechanistically, BghiP exposure upregulated the expression of cytochrome P450 (CYP1A1), which subsequently promoted the transcription of chimeric RNA RPL17-C18orf32. We identified that the CYP1A1/RPL17-C18orf32 axis plays a pivotal role in mediating BghiP's toxic effects. Knockdown of either CYP1A1 or RPL17-C18orf32 attenuated BghiP-induced cytotoxicity, DNA damage, and cellular dysfunction, while overexpression of RPL17-C18orf32 exacerbated these detrimental effects. Co-manipulation experiments further confirmed that CYP1A1 acts upstream to regulate RPL17-C18orf32 expression. This study is the first to provide evidence that the CYP1A1/RPL17-C18orf32 axis is a critical mediator of BghiP-induced respiratory toxicity and DNA damage. Our findings systematically elucidate the cytotoxic and genotoxic effects of BghiP, introducing the novel concept of chimeric RNA involvement in PAH toxicity mechanisms and offering a new perspective for understanding the health impacts of environmental pollutants.
研究领域:
毒理学
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环境健康
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分子生物学
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遗传毒性
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呼吸系统
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MOLECULAR MEDICINE
·
2023
·Vol. 29
·期 1
·1-17
·
IF 5.7
Feng Yuqing,Lu Jinfang,Peng Xujun,Ge Yanni,Zhang Ran,Li Huiling
Background Retinal ganglion cells (RGCs) apoptosis is a vital manifestation of retinal ischemia/reperfusion (I/R) injury, yet the underlying mechanisms are not well understood. The contribution of long noncoding RNAs (lncRNAs) to this cellular process is currently being explored. Based on a lncRNA chip assay, we aimed to investigate the role of lncRNA uc007nnj.1 in the pathological process of ischemia-induced RGCs apoptosis.Methods Hank’s balanced salt solution containing 10 µM antimycin A and 2 µM calcium ionophore for 2 h to construct an ischemic model in RGCs, and elevation of intraocular pressure to 120 mm Hg for 1 h was used to construct a mouse model of retinal I/R injury.Results In this study, lncRNA uc007nnj.1 was highly upregulated in response to I/R injury in RGCs and mouse retinas. In addition, lncRNA uc007nnj.1 knockdown reduced retinal neuronal cell apoptosis in vitro and in vivo and significantly improved retinal function.DiscussionMechanistically, the results demonstrated that lncRNA uc007nnj.1 acts as ceRNA competitively binding miR-155-5p, thereby enhancing the expression levels of Tle4, thus aggravating ischemia-related apoptosis in RGCs.Conclusion sFinally, our study identifies the lncRNA uc007nnj.1/miR-155-5p/Tle4 axis as a potential target for the prevention of I/R-induced retinal neuronal death.
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Frontiers in Immunology
·
2022
·
IF 8.786
Qin Sheng,Huang Xianzhang,Qu Shaogang
Respiratory syncytial virus (RSV) infection is the most frequent cause of hospitalization in pediatric patients. Current systemic treatment and vaccines are not curative and re-infection is often associated with a more drastic incidence of the disease. Baicalin is a flavonoid isolated from Scutellaria baicalensis with potent anti-viral characteristics, namely against RSV. However, its precise mechanism of action remains unclear. Here, using in vitro methods and an in vivo murine model of RSV infection, we showed that baicalin inhibits RSV replication induces translational upregulation of type I interferons (IFNs), IFN-α and IFN-β, and reverses epithelial thickening in lung tissues. Moreover, baicalin inhibits transcription of the RSV non-structural proteins NS1 and NS2. Molecular docking and surface plasmon resonance-based affinity analysis showed that baicalin also binds to the α3 helix of the NS1 protein with an affinity constant of 1.119 × 10−5 M. Polysome profiling showed that baicalin inhibits translation of the RSV matrix protein (M) RNA. Baicalin mediates increased release of the ribosomal protein L13a from the large ribosomal subunit, where the extra ribosomal subunit L13a inhibits M RNA translation. These results comprehensively establish the multiple mechanisms by which baicalin induces a potent innate immune response against RSV infection.
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