Oncogenesis
·
2026
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IF 6
Shen Tao,Ma Yuejiang,Wu Tingting,Cao Zhu,Yi Peng,Huang Xiufeng,Yang Shizhou
High-risk human papillomavirus (HPV) is a causal factor in cervical cancer, driving the cancer’s initiation and progression. Although cancer stem cells (CSCs) have been implicated in maintaining the stemness and malignancy of cervical cancer cells, the underlying mechanisms are not yet fully understood. In this study, we modulated gene expression in Caski and SiHa cervical cancer cells using siRNA and overexpression approaches. Functional assays, including MTT, transwell, RT-qPCR, western blotting, immunohistochemistry, luciferase reporter, immunofluorescence, and sphere formation, were performed to evaluate target gene expression. Additionally, transcriptome sequencing was used to analyze the impact of silencing HPV16 E7 on SiHa cells, and a xenograft model was assessed for in vivo effects. Our transcriptome sequencing reveals substantial changes in gene expression profiles upon HPV16 E7 silencing in cervical cancer. Notably, we identified APC2 as a key downstream target transcriptionally activated by HPV16 E7 through the transcription factor E2F1, and its elevated expression is associated with poor prognosis in cervical cancer. Surprisingly, APC2 exhibits oncogeneic properties in cervical cancer by activating the Wnt/β-catenin pathway, and its overexpression reverses the inhibitory effects of HPV16 E7 silencing on malignancy and CSC properties. Additionally, SPIN4 is identified as a pivotal downstream target of the HPV16 E7/APC2 axis, positively modulating cervical cancer progression. Our study reveals a novel HPV16 E7-APC2-SPIN4 axis as a key driver of cervical cancer. In this pathway, APC2 unexpectedly functions as an oncogene by activating the Wnt/β-catenin signaling to promote tumorigenesis and CSC properties.
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PubMed
高影响因子
BIOCHEMICAL GENETICS
·
2025
·
IF 1.6
Yang Min,Ma Yuejiang,Cao Zhu,Zhan Hong,Jin Ye,Huang Xiufeng,Yang Shizhou
Cervical cancer (CC) is one of the most prevalent cancers among women globally. The primary cause of CC is persistent infection with high-risk types of human papillomavirus (HPV), particularly HPV16, whose E7 oncoprotein plays a pivotal role in carcinogenesis and the maintenance of stem cell-like characteristics. RTKN2 participates in the progression of various cancers. However, the precise functions of RTKN2 in regulating CC remain unclear. The effects of HPV16 E7 in CC cells were evaluated using MTT, western blotting, Transwell, and sphere formation assays. Transcriptome sequencing and bioinformatics analyses were used to identify the targets of HPV16 E7. The expression levels of the target (RTKN2) in clinical samples were assessed using immunohistochemistry (IHC). The function and mechanism of RTKN2 in CC cells were investigated by the knockdown and overexpression approaches, as well as dual-luciferase reporter assay. HPV16 E7 exhibited a positive correlation on the malignant phenotype and stemness of CC cells. RTKN2 was identified as a target of HPV16 E7, and a reduction in its expression levels was caused by knockdown of HPV16 E7. The high expression of RTKN2 was associated with a poor prognosis in CC. HPV16 E7 may regulate RTKN2 expression by modulating the binding activity of E2F1 to the RTKN2 promoter. Upregulated RTKN2 activates the NF-κB signaling pathway, enhances the stemness of CC cells, and ultimately promotes malignant progression.
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PubMed
高影响因子
Journal of Materials Chemistry C
·
2022
·Vol. 10
·期 16
·6435-6443
·
IF 8.067
Xu Sang,Qingru Wang,Xiaoli Gao,Adnan Khan,Ziyu Chen,Jiaxin Yang,Ming Feng,Lisa Liu,Feng Song,Wei Huang
Based on the interaction between Eu(III) complexes and liquid crystals (LCs), three general approaches by using energy transfer, electric field controllable orientation of LCs and the multi-wavelength excitation are presented to obtain a tunable emitting color for rare earth (RE)/LC composites. The Eu(tta)3phen/E7 composites were prepared via a simple guest–host method. The interaction between the RE complexes and LCs is analyzed for the emitting color change of the composites. The E7 host not only facilitates the ultraviolet photon harvesting and subsequent energy transfer to Eu(tta)3phen, but also serves the regulation of the distortion of the symmetry around the Eu3+ ions. Experimental and Judd–Ofelt theoretic analysis of the Eu(tta)3phen/E7 composites indicates the improvement of the luminescence for Eu(tta)3phen in the anisotropic LC host. This modulation of emitting color for RE/LC composites may open the door to broaden the applications of RE ion doped materials.
研究领域:
材料科学
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光学材料
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液晶技术
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发光与光子学
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DOI
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2022
·
IF 6.064
Wu Shuo,Wang Zongliang,Wang Yu,Guo Min,Zhou Mengyang,Wang Liqiang,Ma Jie,Zhang Peibiao
Mesenchymal stem cells (MSCs) have considerable value in regenerative medicine because of their unique properties such as pluripotency, self-renewal ability, and low immunogenicity. Isolation and purification are prerequisites for various biomedical applications of MSCs, and traditional sorting methods are often expensive, complicated, and difficult to apply on a large scale. In addition to purification, the requirement for expansion of cells also limits the further application of MSCs. The purpose of this study was to develop a unique magnetic sorting microsphere to obtain relatively pure and high-yield MSCs in an economical and effective way, that can also be used for the expansion of MSCs. Poly (ethylene glycol) (PEG)-based anti-adhesive treatment of the prepared oleic acid grafted Fe3O4-poly (lactic-co-glycolic acid) magnetic microspheres was performed, and then E7 peptide was covalently grafted onto the treated microspheres. Upon a series of characterization, the magnetic microspheres were of uniform size, and cells were unable to adhere to the PEG-treated surface. E7 grafting significantly improved cell adhesion and proliferation. The results obtained from separate culture of various cell types as well as static or dynamic co-culture showed that selective adhesion of MSCs was observed on the magnetic sorting microspheres. Furthermore, the cells expanded on the microspheres maintained their phenotype and typical differentiation potentials. The magnetic properties of the microspheres enabled sampling, distribution, and transfer of cells without the usage of trypsin digestion. And it facilitated the separation of cells and microspheres for harvesting of MSCs after digestion. These findings have promising prospects for MSC research and clinical applications.
研究领域:
再生医学
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干细胞生物学
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生物医学工程
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PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Ya Zhang,Jianwei Bao,Chen Jiang,Yuhong Liu,Shasha Peng,Qianli Zou
Antigen peptide-based immunotherapy holds significant promise for tumor treatment by eliciting targeted immune responses against tumor cells. However, current methods often face limitations in achieving effective antigen delivery and immune activation. Addressing these challenges through novel delivery systems and immunomodulatory strategies is crucial for improving the clinical efficacy of this therapy. Herein, a supramolecular system based on the self-assembly of the human papillomavirus (HPV) E7 antigen peptide is established by utilizing a Schiff base-mediated self-assembly approach. The E7 antigen peptide nanoparticles (E7 NPs) are further functionalized by loading chlorin e6 (Ce6) and decorating with bovine serum albumin (BSA), generating BSA/E7/Ce6 NPs. The BSA/E7/Ce6 NPs exhibited remarkable photodynamic effects in the inhibition of tumor cells and significantly improved tumor accumulation. Especially, the BSA/E7/Ce6 NPs improved antitumor immune responses of the E7 antigen by effectively activating cytotoxic T lymphocytes. The combination therapy integrating BSA/E7/Ce6 NPs with photodynamic therapy demonstrated a 1.8-fold increase in CD3+CD8+ T cells compared to monotherapy groups, leading to significantly enhanced antitumor effects. Our findings demonstrate that supramolecular antigen peptide nanomaterials can be established as drug delivery systems while retaining their original antigenicity, providing a versatile strategy for realizing enhanced antitumor immunotherapy.
研究领域:
肿瘤学
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免疫学
·
纳米医学
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PubMed
高影响因子
Frontiers in Pharmacology
·
2021
·
IF 5.811
Hao Xincai,Sun Xiaodong,Zhu Haizhen,Xie Lixia,Wang Xuanbin,Jiang Nan,Fu Pan,Sang Ming
Trans-resveratrol (RES) exhibits a wide range of biological activities. Various methodological approaches have been established to improve the pharmacokinetic properties of RES. Moreover, additional in vivo studies are required to support clinical application. In this study, RES/HP-β-CD (RHSD) inclusion complex was prepared and characterized by FTIR, PXRD, DSC and NMR data. The effect and potential mechanism of RHSD against cervical cancer were investigated in a mouse xenograft tumor model by qPCR assay, Western blot assay, and immunohistochemical assay. Results showed that RHSD significantly decreased tumor growth compared with free RES, while the effect of preventing tumor growth was more prominent in vivo. Notably, RHSD could inhibit tumor development by suppressing the expression of HPV E6 and E7 oncogenes and upregulating P53 and Rb1 protein in cervical cancer. These findings demonstrated that RHSD was safe and potential for development of a new oral administration drug to treat cervical cancer.
研究领域:
药理学
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肿瘤学
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药物递送系统
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PubMed
高影响因子
Bioactive Materials
·
2020
·
IF 8.724
Wei Zhang,Chen Ling,Aini Zhang,Haoyang Liu,Yujie Jiang,Xiaolong Li,Renwang Sheng,Qingqiang Yao,Jialin Chen
Endogenous repair of osteochondral defect is usually limited by the insufficient number of cells in the early stage and incomplete cell differentiation in the later stage. The development of drug delivery systems for sequential release of pro-migratory and pro-chondrogenic molecules to induce endogenous bone marrow-derived mesenchymal stem cells (BMSCs) recruitment and chondrogenic differentiation is highly desirable for in situ osteochondral regeneration. In this study, a novel, all-silk-derived sequential delivery system was fabricated by incorporating the tunable drug-loaded silk fibroin (SF) nanospheres into a SF porous matrix. The loading efficiency and release kinetics of biomolecules depended on the initial SF/polyvinyl alcohol (PVA) concentrations (0.2%, 1% and 5%) of the nanospheres, as well as the hydrophobicity of the loaded molecules, resulting in controllable and programmed delivery profiles. Our findings indicated that the 5% nanosphere-incorporated matrix showed a rapid release of E7 peptide during the first 120 h, whereas the 0.2% nanosphere-incorporated matrix provided a slow and sustained release of Kartogenin (KGN) longer than 30 days. During in vitro culture of BMSCs, this functional SF matrix incorporated with E7/KGN nanospheres showed good biocompatibility, as well as enhanced BMSCs migration and chondrogenic differentiation through the release of E7 and KGN . Furthermore, when implanted into rabbit osteochondral defect, the SF nanosphere matrix with sequential E7/KGN release promoted the regeneration of both cartilage and subchondral bone. This work not only provided a novel all-silk-derived drug delivery system for sequential release of molecules, but also a functional tissue-engineered scaffold for osteochondral regeneration.
研究领域:
生物材料
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组织工程
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药物递送系统
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再生医学
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PubMed
高影响因子
Aggregate
·
2024
·
IF 13.9
Yi Long,Shurui Tao,Dongni Shi,Xingyu Jiang,Tian Yu,Yingxi Long,Libing Song,Guozhen Liu
Developing the sensitive point-of-care testing (POCT) of oncogenic nucleic acids from human papillomavirus (HPV) infection is essential in preventing cervical cancer, especially in resource-limited settings. Rolling circle amplification (RCA) is attractive in achieving POCT via nucleic acid-based aggregation under isothermal conditions. However, the influence of RCA product structure on the aggregation remains unexplored resulting in limited sensitivity. Here, a minimum secondary structured RCA technique (MSS-RCA) is developed by designing a unique circular template, demonstrating significantly enhanced detection sensitivity with only one amplification step and one primer under isothermal conditions. The amplification efficiency of MSS-RCA could be kinetically manipulated by controlling the secondary structure of the circular template. Introducing the invertase probe to MSS-RCA, HPV16 E6/E7 nucleic acid target was detected with a personal glucose meter (PGM) with a sensitivity of 5 f m (50 zmol in 10 µL). This integrated MSS-RCA-PGM detection system was successfully applied to detect HPV16 E6/E7 mRNA extracted from 54 cervical swab samples reaching a positive predictive value of 100.00% and negative predictive values of 96.00% (77.77% to 99.40%, 95% CI). MSS-RCA-PGM provides a sensitive POCT platform for the detection of nucleic acid biomarkers for screening of cervical cancer or other diseases.
研究领域:
分子生物学
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癌症筛查
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即时诊断
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核酸扩增
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高影响因子
Biosensors-Basel
·
2024
·Vol. 14
·期 12
·618
·
IF 4.9
Shurui Tao,Yi Long,Guozhen Liu
The Phi29 DNA polymerase is renowned for its processivity in synthesizing single-stranded DNA amplicons by rolling around a circularized DNA template. However, DNA synthesis rolling circle amplification (RCA) is significantly hindered by the secondary structure in the circular template. To overcome this limitation, an engineered circular template without secondary structure could be utilized to improve the sensitivity of RCA-based assays without increasing its complexity. We herein proposed an entropy-driven special RCA technology for the detection of HPV16 E7 gene at room temperature. The strategy is composed of a molecular beacon containing a loop region for nucleic acid target recognition and a stem region to initiate RCA. With the target analyte, the stem region of the molecular beacon will be exposed and then hybridized with a special circular template to initiate the DNA amplification. We tested different designs of the molecular beacon sequence and optimized the assay’s working conditions. The assay achieved a sensitivity of 1 pM in 40 min at room temperature. The sensitivity of this assay, at 1 pm, is about a hundred-fold greater than that of conventional linear RCA performed in solution. Our proposed sensor can be easily reprogrammed for detecting various nucleic acid markers by altering the molecular beacon’s loop. Its simplicity, rapid assay time, and low cost make it superior to RCA sensors that utilize similar strategies.
研究领域:
分子生物学
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生物技术
·
纳米技术
·
分析化学
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PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2021
·
IF 10.618
Guolin Hong,Zhiyan Zou,Zhongnan Huang,Haohua Deng,Wei Chen,Huaping Peng
Persistent high-risk human papillomavirus (HPV) infection is the leading cause of cervical cancer. Efficient detection of HPV16 E7 is necessary for early diagnosis and cure of the disease. Here, a novel and high-performance Au nanocluster (AuNC) probe-based split-type electrochemiluminescent (ECL) assay platform has been established to detect these oncogenes , in which the nucleic acid hybridization assay and the ECL measurements are performed independently. The proposed approach combines superior magnetic nanobead enrichment and separation technology, specific nucleic acid hybridization technology, and high-efficiency AuNC probe ECL strategy, and shows excellent advantages. First, the split-type ECL sensing platform can effectively avoid interference from biological samples and adequately uses the ECL efficiency of the AuNC probe. Furthermore, the ultrahigh sensitivity assay of HPV DNA can be achieved without any complex nucleic acid amplification technique. Taking advantage of the above merits of split-type detection, the ECL DNA sensor achieved ideal low detection of 6.8 aM and a wide dynamic range bridging 10 orders of magnitude HPV16 E7. Furthermore, together with its favorable and powerful specificity, high sensitivity, and good selectivity , this strategy could detect HPV16 E7 DNA in human samples, which showed great consistency with the FDA-approved approach (Hybrid capture 2, HC2). Therefore, this work proposes a facile and reliable split-type ECL platform for HPV diagnosis and shows great potential for the early diagnosis of other diseases.
研究领域:
生物医学工程
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分子生物学
·
分析化学
·
纳米技术
·
癌症研究
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PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2020
·
IF 7.727
Xueqin Gao,Zhuang Jin,Xiangyu Tan,Chong Zhang,Chenming Zou,Wei Zhang,Jiahui Ding,Bhudev C. Das,Konstantin Severinov,Inga Isabel Hitzeroth,Priya Ranjan Debata,Dan He,Xin Ma,Xun Tian,Qinglei Gao,Jun Wu,Rui Tian,Zifeng Cui,Weiwen Fan,Zhaoyue Huang,Chen Cao,Yuxian Bao,Songwei Tan,Zheng Hu
Persistent high-risk HPV infection is the main factor for cervical cancer . HPV E7 oncogene plays an important role in HPV carcinogenesis. Down-regulation of E7 oncogene expression could induce growth inhibition in HPV-positive cells and thus treats HPV related cervical cancer. Here we developed a non-virus gene vector based on poly(amide-amine)-poly(β-amino ester) hyperbranched copolymer (hPPC) for the delivery of CRISPR/Cas9 system to specifically cleave HPV E7 oncogene in HPV-positive cervical cancer cells. The diameter of polyplex nanoparticles (NPs) formed by hPPCs/linear poly(β-amino ester) (PBAE) and plasmids were approximately 300 nm . These hPPCs/PBAE-green fluorescence protein plasmids polyplex NPs showed high transfection efficiency and low toxicity in cells and mouse organs. By cleaving HPV16 E7 oncogene, reducing the expression of HPV16 E7 protein and increasing intracellular retinoblastoma 1 (RB1) amount, hPPCs/PBAE-CRISPR/Cas9 therapeutic plasmids polyplex NPs, especially highly branched hPPC1-plasmids polyplex NPs, exhibited strong growth inhibition of cervical cancer cells in vitro and xenograft tumors in nude mice . Together, the hPPCs/PBAE polyplex NPs to deliver HPV16 E7 targeted CRISPR/Cas9 system in this study could potentially be applied to treat HPV-related cervical cancer.
研究领域:
癌症研究
·
基因治疗
·
纳米技术
·
分子生物学
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PubMed
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Yan Zhao,Huan Wang,Yang Yang,Wendan Jia,Tong Su,Yuxin Che,Yixin Feng,Xuemei Yuan,Xuelian Wang
Background Previously, we demonstrated the therapeutic efficacy of a human papillomavirus (HPV) vaccine, including HPV16 E7 peptide and CpG oligodeoxynucleotides (CpG ODN), against small TC-1 grafted tumors. Here, we developed an HPV16 E7 peptide and CpG ODN vaccine delivered using liposomes modified with DC-targeting mannose, Lip E7/CpG, and determined its anti-tumor effects and influence on systemic immune responses and the tumor microenvironment (TME) in a mouse large TC-1 grafted tumor model.Methods L-alpha-phosphatidyl choline (SPC), cholesterol (CHOL), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol-2000)] (DSPE-PEG-2000), 1,2-dioleoyl-3-trimethylammonium-propane chloride salt (DOTAP) and Mannose-PEG-DSPE, loaded with HPV16 E7 peptide and CpG ODN, were used to construct the Lip E7/CpG vaccine. The anti-tumor effects and potential mechanism of Lip E7/CpG were assessed by assays of tumor growth inhibition, immune cells, in vivo cytotoxic T lymphocyte (CTL) responses and cytokines, chemokines, CD31, Ki67 and p53 expression in the TME. In addition, toxicity of Lip E7/CpG to major organs was evaluated.Results Lip E7/CpG had a diameter of 122.21±8.37 nm and remained stable at 4°C for 7 days. Co-delivery of HPV16 E7 peptide and CpG ODN by liposomes exerted potent anti-tumor effects in large (tumor volume ≥200mm3) TC-1 grafted tumor-bearing mice with inhibition rates of 80% and 78% relative to the control and Free E7/CpG groups, respectively. Vaccination significantly increased numbers of CD4+ and CD8+ T cells, and IFN-γ-producing cells in spleens and tumors and enhanced HPV-specific CTL responses, while reducing numbers of inhibitory cells including myeloid-derived suppressor cells and macrophages. Expression of cytokines and chemokines was altered and formation of tumor blood vessels was reduced in the Lip E7/CpG group, indicating possible modulation of the immunosuppressive TME to promote anti-tumor responses. Lip E7/CpG did not cause morphological changes in major organs.Conclusion Lip E7/CpG induced anti-tumor effects by enhancing cellular immunity and improving tumor-associated immunosuppression. Mannose-modified liposomes are the promising vaccine delivery strategy for cancer immunotherapy.
研究领域:
免疫学
·
肿瘤学
·
药剂学
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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）