INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2012
·Vol. 13
·期 5
·5818-5831
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IF 2.598
Kun Liu,Feng Liu,Nannan Zhang,Shiying Liu,Yuyang Jiang
Pokemon is an important proto-oncogene that plays a critical role in cellular oncogenic transformation and tumorigenesis. Anoikis, which is regulated by Bim-mediated apoptosis, is critical to cancer cell invasion and metastasis. We investigated the role of Pokemon in anoikis, and our results show that Pokemon renders liver cells resistant to anoikis via suppression of Bim transcription. We knocked-down Pokemon in human hepatoma cells QGY7703 with small interfering RNAs (siRNA). Knockdown of Pokemon alone did not significantly affect the growth and survival of QGY7703 cells but notably enhanced their sensitivity to apoptotic stress due to the presence of chemical agents or cell detachment, thereby inducing anoikis, as evidenced by flow cytometry and caspase-3 activity assays. In contrast, ectopic expression of Pokemon in HL7702 cells led to resistance to anoikis. Dual-luciferase reporter and ChIP assays illustrated that Pokemon suppressed Bim transcription via direct binding to its promoter. Our results suggest that Pokemon prevents anoikis through the suppression of Bim expression, which facilitates tumor cell invasion and metastasis. This Pokemon-Bim pathway may be an effective target for therapeutic intervention for cancer.Keywords:Pokemon;anoikis;Bim;hepatoma
研究领域:
肿瘤学
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分子生物学
·
细胞生物学
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DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2022
·
IF 8.008
Qiong Hu,Jianwen Wan,Yilin Luo,Shiqi Li,Xiaojing Cao,Wenxing Feng,Yiyi Liang,Wei Wang,Li Niu
In view of their high efficiency and cost-effectiveness, polymers are of great promise as carriers for signal tags in amplified detection. Herein, we present a polysaccharide-amplified method for the electrochemical detection of a BRCA1 breast cancer gene-derived DNA target at the femtomolar levels. Briefly, peptide nucleic acid (PNA) with a complementary sequence was tethered as the capture probe for the DNA target, to which carboxyl group-containing polysaccharides were then attached via facile phosphate-Zr(IV)-carboxylate crosslinking, followed by the decoration of polysaccharide chains with electroactive ferrocene (Fc) signal tags via affinity coupling between a cis-diol site and phenylboronic acid (PBA) group. As the polysaccharide chain contains hundreds of cis-diol sites, boronate affinity can enable the site-specific decoration of each polysaccharide chain with hundreds of Fc signal tags, efficiently transducing each target capture event into the decoration of many Fc signal tags. As polysaccharides are cheap, renewable, ubiquitous, and biodegradable natural biopolymers, the use of polysaccharides for signal amplification offers the benefits of high efficiency, cost-effectiveness, excellent biocompatibility, and environmental friendliness. The linear range of the polysaccharide-amplified method for DNA detection was demonstrated to be from 10 fM to 10 nM (R2 = 0.996), with the detection limit as low as 2.9 fM. The results show that this method can also discriminate single base mismatch with satisfactory selectivity and can be applied to DNA detection in serum samples. In view of these merits, the polysaccharide-amplified PNA-based electrochemical method holds great promise in DNA detection with satisfactory sensitivity and selectivity.
研究领域:
生物化学
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分子生物学
·
分析化学
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DOI
PubMed
高影响因子
RSC Advances
·
2019
·Vol. 9
·期 17
·9613-9619
·
IF 3.049
Jimin Yang,Lei Gao,Cheng Peng,Wei Zhang
In this work, a novel self-signal DNA electrochemical biosensor was constructed based on tungsten disulfide (WS2) nanosheets combined with poly(indole-6-carboxylic acid) (PIn6COOH) as the sensing interface. The WS2 nanosheets were synthesized via a simple solvent exfoliation method from bulk WS2, and then PIn6COOH was electropolymerized on the WS2 nanosheet-modified carbon paste electrode to obtain a unique nanocomposite. The electropolymerization efficiency was remarkably improved, ascribed to the physical adsorption between WS2 nanosheets and aromatic In6COOH monomers, resulting in an increase of the electrochemical response of PIn6COOH. Owing to the presence of π–π interactions between the conjugated PIn6COOH/WS2 nanocomposite and DNA bases, the probe ssDNA was noncovalently assembled on the nanocomposite substrate. After the hybridization of the probe ssDNA with the target DNA, the formation of the double-helix structure induced the resulting dsDNA to be released from the surface of the conjugated nanocomposite, accompanied with the self-signal regeneration of the nanocomposite (“signal-on”). The constructed PIn6COOH/WS2 nanocomposite was not only employed as an interface for DNA immobilization but also reflected the signal transduction stemming from DNA immobilization and hybridization without any external indicators or complex labeling processes. A detection limit of 2.3 × 10−18 mol L−1 has been estimated and a dynamic range of 1.0 × 10−17 mol L−1 to 1.0 × 10−11 mol L−1 has been shown for the detection of a PIK3CA gene related to lung cancer. Selectivity of the biosensor has been researched in the presence of noncomplementary and base mismatched DNA sequences.
研究领域:
生物传感技术
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医学诊断
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纳米材料科学
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DOI
PubMed
高影响因子
Journal of Biomedical Nanotechnology
·
2018
·Vol. 14
·期 1
·150-160
·
IF 5.068
Li Taotao,Yi Huan,Liu Yuan,Wang Zunliang,Liu Shiquan,He Nongyue,Liu Hongna,Deng Yan
DNA strands have been used as templates to form different sized silver nanoclusters. Although DNA templated silver nanoclusters (NCs) probes which show outstanding fluorescence properties have been widely applied in chemical sensing and cellular imaging, synthesis of DNA template Au–Ag
bimetallic nanoclusters remains a challenge. A facile one-step synthesis method was thus developed in this study to form Au–Ag NCs using C4-ATAT-C4 as template. C4-ATAT-C4 acted as a stabilizer for preventing aggregation of the Au–Ag NCs. The obtained Au–Ag NCs stabilized
by C4-ATAT-C4 showed bright fluorescence and high stability. A series of experiments showed that temperature, citrate-citric acid buffer, sequence and concentration of DNA played an important role in the synthesis of fluorescent Au–Ag NCs. In addition, a ratiometric fluorescence probe
was designed through combining the nucleotide sequence (C4-ATAT-C4) and hybridization sequence in the presence of the double-strand-chelating dye Super SYBR Green (SG). The combination of prepared Au–Ag NCs, Super SG, and perfectly matched DNA emitted fluorescence at 500 and 590 nm,
respectively, when the composite was excited at 290 nm. A gastric cancer gene was also selectively detected by our developed ratiometric fluorescence probe.
研究领域:
生物化学
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纳米生物学
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分子诊断
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DOI
PubMed
高影响因子
APL Photonics
·
2024
·Vol. 9
·期 9
·
IF 5.4
Yin Zhiyong,Jing Xili,Li Shuguang
As an essential biomarker for diagnosing and treating various diseases, low-cost, quantitative detection methods for complementary DNA (cDNA) have received much attention. The surface plasmon resonance (SPR) sensing technique is an effective measurement scheme, but the ambient temperature and pH variations have a non-negligible impact. In this work, we developed a triple-probe SPR sensing system for detecting cDNA concentration, temperature, and pH. In order to satisfy the triple parameter measurements, we used a microstructured optical fiber as the sensing platform, silver and gold films as the excitation layer, and a MoS 2 film as the modulation layer. First, we explore the modulation mechanism of SPR and the conditions for excitation of triple SPR and demonstrate that the carrier concentration is a crucial factor affecting the resonance wavelength. Then, the feasibility of the sensing system for triple-probing is theoretically analyzed. Finally, in the experiment, the optimal parameters of the sensor were determined, and the triple parameter detection was successfully realized. The experimental results show that the three probes can work independently, and the hybridized DNA probe can realize the selective detection of cDNA with a sensitivity of 0.249 nm/(nmol/l). The maximum sensitivity of the pH probe and the temperature probe are 51.5 nm/pH and 6.14 nm/°C. In addition, the experimental results show that the sensing probes have excellent reproducibility. This paper’s innovation is using the fiber optic SPR effect to achieve quantitative detection for cDNA, temperature detection, and pH detection. Therefore, the sensor has a promising future in early diagnosis and biosensing.
研究领域:
生物医学工程
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分子诊断
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纳米技术
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DOI
高影响因子
Journal of Genetics and Genomics
·
2021
·
IF 4.275
Shunqi Pei,Xuehui Wang,Xuan Wang,Hao Huang,Huaping Tao,Binghua Xie,Aifen Yang,Mengsheng Qiu,Zhou Tan
Glioma is the most common type of tumor in the central nervous system, accounting for around 80% of all malignant brain tumors. Previous studies showed a significant association between nuclear morphology and the malignant progress of gliomas. By virtue of integrated proteomics and genomics analyses as well as experimental validations, we identify three nuclear lamin genes ( LMNA , LMNB1 , and LMNB2 ) that are significantly upregulated in glioma tissues compared with normal brain tissues. We show that elevated expressions of LMNB1 , LMNB2 , and LMNA in glioma cells are highly associated with the rapid progression of the disease and the knockdown of LMNB1 , LMNB2 , and LMNA dramatically suppresses glioma progression in both in vitro and in vivo mouse models. Moreover, the repression of glioma cell growth by lamin knockdown is mediated by the pRb-mediated G1-S inhibition. On the contrary, overexpression of lamins in normal human astrocytes dramatically induced nuclear morphological aberrations and accelerated cell growth. Together, our multi-omics-based analysis has revealed a previously unrecognized role of lamin genes in gliomagenesis, providing a strong support for the key link between aberrant tumor nuclear shape and the survival of glioma patients. Based on these findings, lamins are proposed to be potential oncogene targets for therapeutic treatments of brain tumors.
研究领域:
神经科学
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肿瘤学
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分子生物学
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基因组学
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蛋白质组学
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产品关联
DOI
PubMed
高影响因子
NEUROPEPTIDES
·
2025
·
IF 2.7
Qiankun Quan,Xinxin Ma,JianJun Feng,Wanni Li,Xi Li
Alzheimer's disease (AD) is a neurodegeneration driven by beta-amyloid (Aβ) deposits in the brain involving autophagy dysfunction. Ginsenoside Rg1, a pharmacologically active compound found in ginseng, has possible therapeutic effects for AD. This study discovered that FGR proto-oncogene (FGR) was a therapeutic target of Rg1 in AD and it was possibly involved in autophagy. C57BL/6 J mice were injected with 5 μL (1 μg/mL) Aβ 1–42 in the right lateral ventricle to establish an AD model. AD mouse hippocampus had high FGR expression. Intragastrically administered Rg1 (40 mg/kg) decreased FGR protein levels in AD mice's hippocampus and improved memory function in AD mice. Both sides of the mice hippocampal fissure were administered with 2 μL lentiviral particles (1 × 10 7 TU) containing FGR overexpression plasmids. FGR overexpression rendered Rg1 ineffectual in restoring memory function and reducing hippocampal neuron damage. We injected 2 μL lentiviral particles (1 × 10 7 TU/mL) containing short hairpin RNA plasmids targeting FGR to the mice hippocampal fissures. FGR knockdown improved spatial memory function of AD mice, reduced hippocampal neuron apoptosis, and prevented Aβ accumulation. HT22 cells were transfected with small interfering RNA targeting FGR. FGR knockdown increased the viability of Aβ 1–42 treated HT22 cells. BACE1 and LC3II/I protein levels were decreased and p62 and SIRT1 were increased in AD mice and cells with FGR knockdown. LC3 was down-regulated after inhibiting FGR expression in Aβ 1–42 treated hippocampal neurons. In conclusion, Rg1 exerts anti-AD functions by targeting FGR and downregulating its expression.
研究领域:
神经生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2016
·Vol. 6
·期 1
·1-8
·
IF 5.228
Lan Jianming,Liu Yingxin,Li Li,Wen Fadi,Wu Fang,Han Zhizhong,Sun Weiming,Li Chunyan,Chen Jinghua
High-sensitivity detection of trace amounts of c-erbB-2 oncogene was reported to be equal to or surpass the ability of CA 15-3 for early diagnosis and/or follow-up recurrent screening of breast cancer. Therefore, in the current study, by using upconversion nanoparticles (UCNPs), rare earth-doped NaYF 4 :Yb 3+ /Er 3+ as the luminescent labels, a upconversion luminescent (UCL) biosensor based on dual-signal amplification of exonuclease III (ExoIII)-assisted target cycles and long-range self-assembly DNA concatamers was developed for the detection of c-erbB-2 oncogene. The proposed biosensor exhibited ultrasensitive detection with limit as low as 40 aM, which may express the potential of being used in trace analysis of c-erbB-2 oncogene and early diagnosis of breast cancer.
研究领域:
生物传感
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癌症诊断
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分子生物学
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DOI
PubMed
高影响因子
American Journal of Cancer Research
·
2021
·
IF 6.166
Xinwei Liu,Dulei Xiang,Chong Xu,Ruonan Chai
EIF3m is the latest identified subunit of the eukaryotic translation initiation factor 3 (eIF3), however, its function in malignant tumor is rarely reported. In the current work, we observed that EIF3m was aberrant over-expressed in lung adenocarcinoma (LADC) tissues and cell lines, and the increased EIF3m level was closely related to the poor clinical outcomes of the LADC patients. The gain- and loss-of-function assays demonstrated the proto-oncogenetic potential of EIF3m in vitro and in vivo . EIF3m induced-malignant phenotype was partly mediated by the up-regulation of CAPRIN1. The biochemical analysis showed that EIF3m could bind to the 5’UTR of CAPRIN1 and positively modulate its expression at the post-transcription level. Furthermore, we identified the interaction between EIF3m and the deubiquitinase UCHL5, which stabilized and promoted the accumulation of EIF3m in LADC cells. In summary, our findings extended the knowledge about the EIF3m function and highlight the roles of the UCHL5/EIF3m/CAPRIN1 axis during the progression of LADC.
研究领域:
肿瘤学
·
分子生物学
·
癌症研究
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产品关联
DOI
PubMed
高影响因子
ARCHIVES OF DERMATOLOGICAL RESEARCH
·
2024
·Vol. 317
·期 1
·1-12
·
IF 1.8
Mu Yanan,Lian Chen,Chen Xinghui,Yang Xueying,Li Dongxia,Zhang Yi
Tumor-derived exosomes that transport MicroRNAs significantly influence cutaneous squamous cell carcinoma(CSCC) progression. However, the molecular mechanisms of exosomal MicroRNA-31 regulation of CSCC are mostly undefined. To determine whether a targeting relationship exists between MicroRNA-31 (miR-31) in CSCC-derived exosomes and the tumor suppressor RhoBTB1, and the regulatory effect of the relationship on tumor cells. Immunoblotting and quantitative PCR were used to measure miR-31 and RhoBTB1 levels in various cells and exosomes. Differential ultracentrifugation was used to isolate exosomes. MTT and Transwell assays were used to assess cell proliferation, migration, and invasion. Dual luciferase reporter assays were used to assess the direct interaction between miR-31 and the tumor suppressor RhoBTB1 in cutaneous squamous cell carcinoma (CSCC)-derived exosomes. Compared with a human skin keratinocyte cell line, in CSCC cell lines RhoBTB1 was downregulated and miR-31 levels were elevated. Exosomal miR-31 from CSCC cell lines directly targeted RhoBTB1 by binding to the 3’ UTR of RhoBTB1. This interaction suppressed expression of RhoBTB1 and enhanced CSCC cell proliferation, migration, and invasion. MicroRNA-31 in CSCC-derived exosomes can enhance CSCC cell proliferation, migration, and invasion by suppressing expression of RhoBTB1. This finding explains, in part, the molecular mechanism of CSCC. Investigative approaches focused on suppressing miR-31 or enhancing RhoBTB1 signaling pathways are promising avenues for developing targeted therapies for CSCC.
研究领域:
肿瘤学
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分子生物学
·
细胞生物学
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DOI
PubMed
高影响因子
Experimental and Therapeutic Medicine
·
2021
·Vol. 22
·期 6
·1-8
·
IF 2.447
Chun Lei,Yafeng Hou,Jiong Chen
Bone marrow stromal cell antigen 2 (BST2) has been reported to act as an oncogene in the tumorigenesis of numerous types of cancer. Bioinformatics analysis has predicted the binding interaction between BST2 and specificity protein 1 (SP1) and the involvement of SP1 in pancreatic cancer. Therefore, the present study set out to verify this interaction and determine how it may affect pancreatic cancer progression. Normal human pancreatic duct epithelial cells (HPDE6‑C7) and pancreatic cancer cell lines (SW1990, BxPC3, PANC1 and PSN‑1) were selected for western blotting and reverse transcription‑quantitative PCR detection of BST2 expression. Colony formation, Cell Counting Kit‑8 and wound healing assays were performed to detect the proliferative and migratory abilities of PANC1 cells following transfection with small interfering RNA against BST2. The expression of proliferation and migration markers were assayed using western blotting. Chromatin immunoprecipitation and luciferase reporter assays were employed to verify the bioinformatics prediction of BST2‑SP1 binding. PANC1 cell proliferation and migration were analyzed following BST2 knockdown and SP1 overexpression. In comparison with HPDE6‑C7 cells, all four pancreatic cancer cell lines were found to exhibit increased BST2 expression levels to varying degrees, with the highest levels observed in PANC1 cells. BST2 knockdown inhibited PANC1 cell colony formation, proliferation and migration. Additionally, SP1 was shown to bind to the BST2 promoter and could promote PANC1 cell proliferation and migration when overexpressed. However, BST2 knockdown rescued SP1 overexpression‑induced PANC1 cell colony formation, proliferation and migration. In conclusion, activation of BST2 by the transcription factor SP1 was shown to accelerate pancreatic cancer cell proliferation and migration, suggesting that BST2 and SP1 may be plausible therapeutic targets in targeted therapy for pancreatic cancer.
研究领域:
肿瘤学
·
分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Pharmaceutical Analysis
·
2024
·
IF 6.1
Xin Yang,Guang-Yuan Ma,Xiao-Qiang Li,Na Tang,Yang Sun,Xiao-Wei Hao,Ke-Han Wu,Yu-Bo Wang,Wen Tian,Xin Fan,Zezhi Li,Caixia Feng,Xu Chao,Yu-Fan Wang,Yao Liu,Di Li,Wei Cao
Hepatocellular carcinoma (HCC) expresses abundant glycolytic enzymes and displays comprehensive glucose metabolism reprogramming. Aldolase A (ALDOA) plays a prominent role in glycolysis; however, little is known about its role in HCC development. In the present study, we aim to explore how ALDOA is involved in HCC proliferation. HCC proliferation was markedly suppressed both in vitro and in vivo following ALDOA knockout, which is consistent with ALDOA overexpression encouraging HCC proliferation. Mechanistically, ALDOA knockout partially limits the glycolytic flux in HCC cells. Meanwhile, ALDOA translocated to nuclei and directly interacted with c-Jun to facilitate its Thr93 phosphorylation by P21-activated protein kinase; ALDOA knockout markedly diminished c-Jun Thr93 phosphorylation and then dampened c-Jun transcription function. A crucial site Y364 mutation in ALDOA disrupted its interaction with c-Jun, and Y364S ALDOA expression failed to rescue cell proliferation in ALDOA deletion cells. In HCC patients, the expression level of ALDOA was correlated with the phosphorylation level of c-Jun (Thr93) and poor prognosis. Remarkably, hepatic ALDOA was significantly upregulated in the promotion and progression stages of diethylnitrosamine-induced HCC models, and the knockdown of ALDOA strikingly decreased HCC development in vivo . Our study demonstrated that ALDOA is a vital driver for HCC development by activating c-Jun-mediated oncogene transcription, opening additional avenues for anti-cancer therapies.
研究领域:
肿瘤学
·
分子生物学
·
癌症研究
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）