Scientific Reports
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2025
·Vol. 15
·期 1
·1-12
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IF 3.9
Huang Rongfu,Yao Jianfeng,Liu Lei,Li Hua,Huang Baoshan
This study investigated the role of LRRC42 in tumor development and progression using comprehensive methodologies. Analysis of RNA-seq data from the TCGA database revealed that LRRC42 expression is upregulated in various tumor tissues, including bladder cancer (BLCA), breast cancer (BRCA), cholangiocarcinoma (CHOL), colorectal cancer (COAD), esophageal cancer (ESCA), glioblastoma (GBM), head and neck squamous cell carcinoma (HNSC), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), and skin cutaneous melanoma (SKCM), compared to normal tissues. Conversely, LRRC42 was significantly downregulated in kidney chromophobe (KICH) and thyroid carcinoma (THCA) tissues. Single-cell analysis using the TISCH2 database highlighted high LRRC42 expression levels in specific subpopulations across different cancers. Correlation analyses indicated associations between LRRC42 expression and prognosis in multiple tumors, linking it to poor overall survival in several cancer types. Investigations into LRRC42’s interactions with the tumor immune microenvironment and signaling pathways demonstrated significant correlations with immune cells, epithelial-mesenchymal transition molecules, autophagy-related factors, and pyroptosis-related molecules. Focusing on LRRC42’s potential role in hepatocellular carcinoma (HCC), the study uncovered co-expression relationships with Th2 cells and identified genes enriched in mRNA processing and cell cycle regulation pathways. Functional validation through LRRC42 knockdown experiments revealed its critical involvement in promoting cell proliferation, migration, and invasion in HCC cell lines. Collectively, these findings emphasize LRRC42 as a promising therapeutic target for inhibiting HCC progression and suggest its pivotal role in modulating key cellular processes integral to HCC advancement.
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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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2019
·
IF 8.456
Weiwei Mu,Dandan Jiang,Shengjun Mu,Shuang Liang,Yongjun Liu,Na Zhang
The specific-targeting approach could promote the specificity of diagnosis and the accuracy of cancer treatment. The choice of a specific-targeting receptor is the key step in this approach. Glypican-3 (GPC3) is an oncofetal proteoglycan anchored on the cell membrane. It is overexpressed even in the early stage of hepatocellular carcinoma (HCC), whereas it shows almost no expression in the healthy adult liver. Therefore, GPC3 may be applied as a specific-targeting receptor for HCC theranostics. In this study, a GPC3 specific-targeting theranostics nanodevice, GPC3 targeting peptide (named G12)-modified liposomes co-loaded with sorafenib (SF) and IR780 iodide (IR780), was developed (GSI-Lip), which aims to realize early diagnosis and precise chemo-photothermal therapy of HCC. SF was the first-line chemotherapy drug for the treatment of HCC. IR780 was used for photothermal therapy and near-infrared fluorescence imaging. The evaluation of early diagnosis verified that early-stage tumors (3.45 ± 0.98 mm3, 2 days after 5 × 105 H22 cells’ inoculation in mice) could be clearly detected using GSI-Lip, which was significantly more sensitive than folic acid-modified liposomes (p < 0.01, 32.90 ± 10.01 mm3, 4 days after 1 × 106 H22 cells’ inoculation in mice). The study of the endocytic pathway indicated that specific G12/GPC3 recognition may induce caveolae-mediated endocytosis of GSI-Lip. Notably, the accumulation of GSI-Lip in tumors was significantly increased compared with that observed with folic acid-modified liposomes (p < 0.01). Specific-targeting endowed the precise antitumor effect of GSI-Lip. GSI-Lip showed a higher antitumor efficacy in comparison with folic acid-modified liposomes (inhibition rate: 90.52% vs 84.22%, respectively; p < 0.01). During a period of 21 days, the synergistic chemo-photothermal therapy (GSI-Lip + laser) exhibited a better antitumor effect versus GSI-Lip without laser (inhibition rate: 94.93% vs 90.52%, respectively; p < 0.01). Overall, GPC3-targeted GSI-Lip promoted the sensitivity and specificity of HCC early diagnosis and achieved synergistic efficacy of chemo-photothermal theranostics, which has potential clinical applications. Furthermore, the present study revealed that a more specific-targeting ligand could further improve the efficacy of theranostics against HCC.
研究领域:
肿瘤学
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分子生物学
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药剂学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2024
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IF 5.3
Chenyu Cao,Yifei Li,Fangzhou Shi,Shanshan Jiang,Yutong Li,Leilei Yang,Xinyi Zhou,Yuqiong Gao,Feiyan Tang,Huan Li,Shulan Han,Zhuo Yu,Yifang Zou,Jianfeng Guo
Doxorubicin (DOX) is a chemotherapy drug used for hepatocellular carcinoma (HCC) treatment, but its effectiveness can be dramatically dampened by cancer cell chemoresistance. Signal transducer and activator of transcription 3 (STAT3) is implicated with drug resistance in a range of cancers (e.g., HCC), and the STAT3 inhibition can reverse the resistance of cancer cells to chemotherapeutic drugs. In the present study, a combination regimen to improve the efficiency of DOX was provided via the STAT3 blockade using plumbagin (PLB). A poly(lactic-co-glycolic acid) decorated by polyethylene glycol and aminoethyl anisamide was produced in the present study with the hope of generating the nanoparticles for co-delivery of DOX and PLB. The resulting co-formulation suppressed the STAT3 activity and achieved the synergistic chemotherapy, which led to tumor inhibition in the mice with subcutaneous DOX-resistant HCC, without causing any toxicity. The present study reveals the synergism of DOX and PLB, and demonstrates a promising combinatorial approach for treating HCC.
研究领域:
肿瘤学
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药理学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
Oncotarget
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2017
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IF 5.168
Jie Gao,Gao-Ju Wang,Zhao Wang,Na Gao,Jing Li,Yun-Fei Zhang,Jun Zhou,Hong-Xin Zhang,Qiang Wen,Han Jin,Hai-Ling Qiao
Hepatofibrosis, which leads to cirrhosis and eventual hepatocellular carcinoma, is a common response to chronic toxin-mediated liver injury. Nitrosamines are potent hepatotoxic agents that cause necrosis and subsequent fibrosis in the liver as a result of cytochrome P450 2E1 (CYP2E1)-dependent metabolism, which generates toxic metabolites that form adducts with nucleic acids, leading to hepatotoxicity and mutagenesis. Herein, CYP2E1 activity and content were determined in fibrotic liver tissue from patients with hepatocellular carcinoma. The relationship between CYP2E1 innate activity and hepatofibrogenesis was evaluated, the effect of inhibition of CYP2E1 activity on hepatofibrosis was determined in a Sprague-Dawley rat model of diethylnitrosamine-induced hepatofibrosis. The results demonstrated that the CYP2E1 activities in human fibrotic tissues are significantly higher than that in normal liver tissues. In rats treated with diethylnitrosamine, the livers demonstrated various degree of fibrotic changes and collagen deposition in individual rats. The Ishak score, which determines the stage of fibrosis, correlated with CYP2E1 innate activity, with greater fibrosis in rat livers with higher CYP2E1 innate activity. Inhibition of CYP2E1 during diethylnitrosamine treatment decreased hepatofibrosis and there was an inverse correlation between the degree of inhibition and the extent of hepatofibrosis. Therefore, high CYP2E1 activity is a risk factor for hepatofibrogenesis induced by nitrosamines.
研究领域:
医学
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毒理学
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肝脏研究
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DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2021
·Vol. 9
·期 22
·4577-4586
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IF 6.331
Yongjia Tang,Haoran Xu,Yaxue Dai,Fang Wang,Wenjing Huang,Peifei Liu,Yueqing Gu
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with limited diagnosis. Mesenchymal epithelial transition factor (c-Met) has become a hot target for cancer diagnosis and therapy, which is overexpressed in HCC. In this study, we labeled a novel c-Met targeting peptide YQ-M3 with a near-infrared fluorescent dye MPA and a radionuclide technetium-99m for HCC detection. YQ-M3-MPA showed high affinity for c-Met positive HepG2 tumor in vitro and higher tumor uptake and higher T/N ratio than GE137-MPA (a positive tracer for c-Met) in HepG2 tumor-bearing mice in vivo by fluorescence imaging. In addition, 99mTc-HYNIC-YQ-M3 also showed significant tumor uptake in vivo through SPECT imaging. These results indicated that c-Met positive tumors were successfully detected via fluorescence and SPECT imaging using YQ-M3-MPA and 99mTc-HYNIC-YQ-M3, respectively, and further suggested that YQ-M3-MPA and 99mTc-HYNIC-YQ-M3 have some possibly potential clinical applications for HCC diagnosis.
研究领域:
肿瘤学
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分子生物学
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医学成像
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产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2024
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IF 6.9
Li Zhang,Lixia Guan,Yuting Wang,Miao-Miao Niu,Jinhu Yan
Dual-specificity tyrosine phosphorylation-regulated kinase 2 (DYRK2) and histone deacetylase 8 (HDAC8) have been shown to be associated with the development of several cancers. Here, we identified a dual-target DYRK2/HDAC8 inhibitor (DYC-1) through a combined virtual screening protocol. DYC-1 exhibited nanomolar inhibitory activity against both DYRK2 (IC 50 = 5.27 ± 0.13 nM) and HDAC8 (IC 50 = 8.06 ± 0.47 nM). Molecular dynamics simulations showed that DYC-1 had positive binding stability with DYRK2 and HDAC8. Importantly, the cytotoxicity assay indicated that DYC-1 exhibited superior antiproliferative activity against human liver cancer, especially SK-HEP-1 cells, and had no significant inhibition on normal liver cells. Moreover, DYC-1 showed a strong inhibitory effect on the growth of SK-HEP-1 xenograft tumors with no significant side effects. These data suggest that DYC-1 is a high-efficacy and low-toxic antitumor agent for the treatment of hepatocellular carcinoma.
研究领域:
肿瘤学
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药物化学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2019
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IF 4.396
Huanling Guo,Ming Xu,Zhong Cao,Wei Li,Lida Chen,Xiaoyan Xie,Wei Wang,Jie Liu
Ultrasound-induced microbubble sonoporation has been shown to effectively improve drug/gene delivery efficiency by enhancing tissue and cell permeability. However, the microscale size and short duration of ultrasound contrast agents limit their accumulation in target areas. Here, a kind of ultrasound-triggered phase-transitioning and size-changing cationic nanodroplet, perfluoropentane/C9F17-PAsp(DET)/miR-122/poly(glutamic acid)-g-MeO-poly(ethylene glycol) (PGA-g-mPEG) ternary nanodroplets (PFP-TNDs/miR-122), was developed to deliver microRNA-122 (miR-122) for hepatocellular carcinoma (HCC) treatment. PFP served as an ultrasound-sensitive core for ultrasound-triggered phase transition and size change from the nanoscale to the microscale. Positively charged C9F17-PAsp(DET) ensured adequate miRNA loading. PGA-g-mPEG, which served as the shell of the nanodroplet, modified the nanodroplets, enhanced their stability in serum, and protected miR-122 from degradation in vivo. The results exhibited that PFP-TNDs/miR-122 has a nanosize diameter (362 ± 15 nm) and remained stable for 24 h. After treatment with PFP-TNDs/miR-122 combined with ultrasound irradiation, the miR-122 expression level was significantly increased by approximately 600-fold in HepG2 cells, 500-fold in SMMC-7721 cells, and 30-fold in human HCC xenografts. Moreover, PFP-TNDs/miR-122 combined with ultrasound radiation effectively suppressed the growth, migration, and invasion of HCC cells, and inhibited tumor proliferation in mice. This study revealed that the biodegradable PFP-TNDs is a promising therapeutic gene carrier with functions of gene protection and effective gene delivery for clinical applications. Furthermore, PFP-TNDs/miR-122 associated with ultrasound irradiation may pave a new way to improve the prognosis of patients with HCC.
研究领域:
医学
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生物技术
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
Journal of Cancer
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2022
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IF 4.478
Kezhong Tang,Qing Chen,Yanmo Liu,Lantian Wang,Wenjie Lu
Hepatocellular carcinoma (HCC) is one of the most lethal cancers in the world. Sorafenib is the first small-molecule multi-kinase inhibitors approved by FDA for treatment of advanced HCC. Metformin has been demonstrated to have benefit for preventing cancer progression. In human recurrent HCCs, NF-E2-related factor 2 (Nrf2) was overexpressed and associated with poor survival. Nrf2 related signaling pathway plays central role to mediate cellular resistance to sorafenib through protecting HCC cells from ferroptosis. The effect of Combination treatment for HCC cells and the intrinsic mechanism have not been reported. In this study, metformin augmented the anti-tumor effect of sorafenib for HCC through ferroptosis induction by inhibiting Nrf2 related pathway. Based on the results of Nrf2 knockdown and p62 knockdown study, the combination of sorafenib and metformin suppressed proliferation of HCC cells through p62-Keap1-Nrf2/HO1 signaling way. Size of xenografts treated with the combination of sorafenib and metformin was smaller than other groups in vivo . Moreover, the combination treatment greatly induced ferroptosis in HCC cells through inhibiting Nrf2 expression. Based on our findings, the combination treatment suppressed proliferation of HCC cells through ferroptosis induction, by p62-Keap1-Nrf2/HO1 signaling way.
研究领域:
肿瘤学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
Molecular Therapy-Nucleic Acids
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2023
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IF 8.8
Yufei Pan,Jing Guan,Yujing Gao,Yuejie Zhu,Huantong Li,Hua Guo,Qianyi He,Zhu Guan,Zhenjun Yang
Antisense oligonucleotides (ASOs) are a class of therapeutics targeting mRNAs or genes that have attracted much attention. However, effective delivery and optimal accumulation in target tissues in vivo are still challenging issues. CT102 is an ASO that targets IGF1R mRNA and induces cell apoptosis. Herein, a detailed exploration of the tissue distribution of ASOs delivered by liposomes was carried out. A formulation that resulted in increased hepatic accumulation was identified based on multiple intermolecular interactions between DCP (cytidinyl/cationic lipid DNCA/CLD and DSPE-PEG) and oligonucleotides, including hydrogen bonding, π-π stacking, and electrostatic interactions. The structurally optimized CT102s present a novel strategy for the treatment of hepatocellular carcinoma. The gapmer CT102 MOE5 and conjugate Glu-CT102 MOE5 showed superior antiproliferation and IGF1R mRNA suppression effects at 100 nM in vitro and achieved greater efficacy at a lower dose and administration frequency in vivo . Combined transcriptome and proteome analyses revealed that additional associated targets and functional regulations might simultaneously exist in ASO therapy. These results showed that a combination of lipid encapsulation and structural optimization in the delivery of oligonucleotide drugs has favorable prospects for clinical application.
研究领域:
分子生物学
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肿瘤学
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
Journal of Inflammation Research
·
2025
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IF 4.1
Qiaohui Ren,Xinyue Zhu,Nannan Wang,Kang Yu,Wei Lv,Lianzi Wang,Yan Zang,Dongyue Ma,Xinyi Zhou,Junxiao Yao,Mengjiao Shen,Li Yu,Tao Li
Purpose We explored the effects of miR-133a-5p and ATP7B on cuproptosis in hepatocellular carcinoma.Methods Initially, we assessed the impact of miR-133a-5p on hepatocellular carcinoma (HCC) using CCK-8 assays, cell scratch assays, and flow cytometry. Subsequently, we utilized elesclomol in combination with copper ions to induce cuproptosis in the HCC cell lines PLC/PRF/5 and Huh-7. We evaluated the influence of miR-133a-5p on cuproptosis using CCK-8 assays, cell scratch assays, flow cytometry, and Western blotting. To elucidate the underlying mechanisms, we employed bioinformatics to identify potential downstream target genes of miR-133a-5p and conducted dual-luciferase reporter assays to confirm the binding sites. Finally, we validated the regulatory effect of miR-133a-5p on ATP7B by modulating miR-133a-5p expression through cell transfection experiments.Results The results from the CCK-8 assay, cell scratch assay, and flow cytometry demonstrated that miR-133a-5p significantly inhibits the proliferation and migration of HCC cells while promoting their apoptosis. Furthermore, Elesclomol in combination with copper ions induces cuproptosis in HCC cells. Compared to the cuproptosis observed in HCC as a control, miR-133a-5p further suppresses the proliferation and migration of HCC cells, enhances their death, and increases the expression of cuproptosis-related proteins more prominently. Bioinformatics analysis suggested that ATP7B might be a downstream target gene of miR-133a-5p. This was confirmed by dual luciferase assays, which identified a binding site between miR-133a-5p and ATP7B. Additionally, the expression levels of ATP7B were found to decrease or increase in response to the regulation by miR-133a-5p.Conclusion MiR-133a-5p facilitates cuproptosis in hepatocellular carcinoma through targeting of ATP7B.
研究领域:
肿瘤学
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分子生物学
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遗传学
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产品关联
DOI
PubMed
高影响因子
International Journal of Pharmaceutics-X
·
2025
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IF 6.4
Yue Yang,Chonggao Wang,Shiwei Liu,Yewei Zhang
This study aimed to create multifunctional nanoparticles (NPs), specifically [email protected] (AMLC), for the purpose of developing effective strategies for treating hepatocellular carcinoma (HCC) through targeted therapy and photothermal therapy (PTT). The study involved synthesizing mesoporous polydopamine (MPDA)-NPs, loading lenvatinib (Len) and Cy5.5 via incubation, and modifying AS1411 aptamer onto MPDA via a covalent chemical reaction. The NPs were characterized using techniques such as ultra-micro spectrophotometry, Fourier transform infrared spectroscopy, and transmission electron microscopy. Target-specific uptake and cell-killing assays were utilized to evaluate AMLC-mediated synergistic therapy while using Western blotting and immunofluorescence to confirm the underlying mechanism. Consequently, the nanoparticles (NPs) were successfully synthesized, demonstrating excellent solvent solubility and stability, with controlled drug release achieved in acidic environments (maximum release efficiency≈80 %). In vitro and in vivo studies revealed that these NPs could more effectively target hepatocellular carcinoma (HCC) cells, enhancing the targeting capability of lenvatinib. Under near-infrared (NIR) laser irradiation, the targeted photothermal therapy (PTT) exhibited significantly improved anticancer efficacy, with AMCL+PTT treatment resulting in up to 76 % tumor volume reduction ( P < 0.01). The study demonstrates that AMLC, a multifunctional nano-delivery system, significantly enhances Lenvatinib's tumor-targeting capacity while exhibiting excellent biocompatibility. Combined with photothermal therapy (PTT), it demonstrates potent antitumor efficacy, showing promising clinical translation potential for hepatocellular carcinoma (HCC) therapy.
研究领域:
肿瘤学
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纳米医学
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药理学
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产品关联
DOI
PubMed
高影响因子
CURRENT MOLECULAR MEDICINE
·
2025
·Vol. 25
·期 3
·343-352
·
IF 2.5
Weiqing Feng,Haixiong Zhang,Qing Yu,Hao Yin,Xiaowei Ou,Jie Yuan,Liang Peng
Background The emergence of treatment resistance has hindered the efficacy of targeted therapies used to treat patients with hepatocellular carcinoma (HCC). Objective This study aimed to explore the mechanism of organoids constructed from lenvatinib-resistant HCC cells. Methods Hep3B cell and human HCC organoids were cultured and identified using hematoxylin and eosin staining and Immunohistochemistry. Lenvatinib-sensitive/ resistant Hep3B cells were constructed using lenvatinib (0, 0.1, 1, and 10 μM) and lenvatinib (0, 1, 10, and 100 μM). qRT-PCR and flow cytometry were utilized to deter-mine HCC stem cell markers CD44, CD90, and CD133 expressions. Transcriptome sequencing was performed on organoids. Western blot evaluated Notch pathway-related proteins (NOTCH1 and Jagged) expressions. Furthermore, DAPT, an inhibitor of the Notch pathway, was used to investigate the effects of lenvatinib on resistance or stemness in organoids and human HCC tissues. Results The organoids were successfully cultivated. With the increase of lenvatinib concentration, sensitive cell organoids were markedly degraded and ATP activity was gradually decreased, while there was no significant change in ATP activity of resistant cell organoids. CD44 expressions were elevated after lenvatinib treatment compared with the control group. KEGG showed that lenvatinib treatment of organoids constructed from Hep3B cells mainly activated the Notch pathway. Compared with the control group, NOTCH1 and Jagged expressions elevated, and ATP activity decreased after lenvatinib treatment. However, ATP activity was notably decreased after DAPT treatment. Moreover, DAPT inhibited lenvatinib resistance and the increase in the expressions of CD44 caused by lenvatinib. Besides, 100 μM lenvatinib significantly inhibited the growth and ATP activity of human HCC organoids, and DAPT increased the inhibitory effect of lenvatinib. Conclusion Lenvatinib regulated resistance and stemness in organoids via the Notch pathway.
研究领域:
肿瘤学
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分子生物学
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转化医学
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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）