Cancer gene therapy最新文献

The antitumor peptide M1-20 induced the degradation of CDK1 through CUL4-DDB1-DCAF1-involved ubiquitination. 抗肿瘤肽 M1-20 通过 CUL4-DDB1-DCAF1 参与的泛素化作用诱导 CDK1 降解。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-11-20 DOI: 10.1038/s41417-024-00855-8

Huitong Bu, Chaozhu Pei, Min Ouyang, Yan Chen, Li Yu, Xiaoqin Huang, Yongjun Tan

引用次数: 0

CEACAM6 facilitates gastric cancer progression through upregulating SLC27A2. CEACAM6 通过上调 SLC27A2 促进胃癌进展。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-11-19 DOI: 10.1038/s41417-024-00846-9

Xiaqiong Mao, Tongtai Liu, Shunying Yu, Yuqi Wei, Chunli Zhou, Xiaoyi Kuai

引用次数: 0

Serum small extracellular vesicles-derived BST2 as a biomarker for papillary thyroid microcarcinoma promotes lymph node metastasis. 血清小细胞外囊泡衍生的BST2是甲状腺乳头状微癌促进淋巴结转移的生物标记物

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-11-18 DOI: 10.1038/s41417-024-00854-9

Zhen Cao, Yuanyang Wang, Jianqiang Wu, Xiaoyue Tang, Zhihong Qian, Zejian Zhang, Rui Liu, Peng Liu, Zepeng Li, Xiequn Xu, Ziwen Liu

{"title":"Serum small extracellular vesicles-derived BST2 as a biomarker for papillary thyroid microcarcinoma promotes lymph node metastasis.","authors":"Zhen Cao, Yuanyang Wang, Jianqiang Wu, Xiaoyue Tang, Zhihong Qian, Zejian Zhang, Rui Liu, Peng Liu, Zepeng Li, Xiequn Xu, Ziwen Liu","doi":"10.1038/s41417-024-00854-9","DOIUrl":"10.1038/s41417-024-00854-9","url":null,"abstract":"Papillary thyroid microcarcinoma (PTMC), although frequently indolent, could be aggressive in a few patients, leading to lymph node metastasis (LNM) and worsened prognosis. To explore the role of protein profiling of small extracellular vesicles (sEVs) in the auxiliary diagnosis and risk stratification of PTMC, proteins in serum sEVs isolated from PTMC patients with (N = 10) and without (N = 10) LNM and benign thyroid nodule (BN) patients (N = 9) were profiled via a bioinformatics-integrated data-independent acquisition proteomic technique. The performance of candidate proteins as diagnostic and prognostic biomarkers in PTMC was assessed via receiver operating characteristic analysis. We found that serum sEVs from PTMC patients promoted the proliferation and migration of human papillary thyroid cancer (PTC) cells and tube formation in human lymphatic endothelial cells (HLECs). SEV proteins from PTMC patients with and without LNM have differential expression profiles, with bone marrow stromal cell antigen 2 (BST2) being best associated with PTMC progression. Through knockdown and overexpression, we proved that the high expression of sEV-derived BST2 was bound up with higher proliferation and migration ability of PTC cells as well as stronger lymphangiogenesis in HLECs. This study brought insight into the differential sEV-protein profile with or without LNM in PTMC. The serum sEV-BST2 may contribute to PTMC progression and LNM and may have diagnostic, prognostic, and therapeutic implications.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ammonia death: a novel potential strategy to augment immunotherapy in cancer. 氨死亡：增强癌症免疫疗法的潜在新策略。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-11-11 DOI: 10.1038/s41417-024-00851-y

Zhi Li, Junyi Lin, Peihao Yin

引用次数: 0

Overexpression of Pin1 regulated by TOP2A, which subsequently stabilizes Pyk2 to promote bortezomib resistance in multiple myeloma. 受TOP2A调控的Pin1过表达，随后稳定Pyk2，从而促进多发性骨髓瘤的硼替佐米耐药性。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-11-07 DOI: 10.1038/s41417-024-00845-w

Honghao Zhang, Jianyu Chen, Yabo Meng, Qingyan Cen, Hao Wang, Xiangyang Ding, Kexin Ai, Yulu Yang, Yang Gao, Yingqi Qiu, Yuxing Hu, Meifang Li, Yanjie He, Yuhua Li

{"title":"Overexpression of Pin1 regulated by TOP2A, which subsequently stabilizes Pyk2 to promote bortezomib resistance in multiple myeloma.","authors":"Honghao Zhang, Jianyu Chen, Yabo Meng, Qingyan Cen, Hao Wang, Xiangyang Ding, Kexin Ai, Yulu Yang, Yang Gao, Yingqi Qiu, Yuxing Hu, Meifang Li, Yanjie He, Yuhua Li","doi":"10.1038/s41417-024-00845-w","DOIUrl":"https://doi.org/10.1038/s41417-024-00845-w","url":null,"abstract":"Multiple myeloma (MM), a hematological malignancy of plasma cells, has remained largely incurable owing to drug resistance and disease relapse, which requires novel therapeutic targets and treatment approaches. Peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 (Pin1) acts as an oncoprotein linked to the development of various tumors. However, the functional consequence of Pin1 overexpression in modulating MM biology has not been established. In the present study, we show that Pin1 expression is highly variable in myeloma cell lines and primary MMs and that high Pin1 expression is associated with poor survival of MM patients. Next, TOP2A is identified to be a Pin1 promoter-binding protein and CK2 activates TOP2A to promote the expression level of Pin1. Additionally, we demonstrate that Pin1 positively modulates the stability and function of Pyk2 to enhance bortezomib resistance in MM. Pin1 recognizes three phosphorylated Ser/Thr-Pro motifs in Pyk2 via its WW domain and increases the cellular levels of Pyk2 in an isomerase activity-dependent manner by inhibiting the ubiquitination and proteasomal degradation of Pyk2. Moreover, Pin1 inhibition combined with Pyk2 inhibition decreases myeloma burden both in vitro and in vivo. Altogether, our findings reveal the tumor-promoting role of Pin1 in MM and provide evidence that targeting Pin1 could be a therapeutic strategy for MM.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Novel pharmacologic inhibition of lysine-specific demethylase 1 as a potential therapeutic for glioblastoma. 新型赖氨酸特异性去甲基化酶 1 药物抑制剂作为胶质母细胞瘤的一种潜在疗法。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-11-05 DOI: 10.1038/s41417-024-00847-8

Keiko Shinjo, Takashi Umehara, Hideaki Niwa, Shin Sato, Keisuke Katsushima, Shinya Sato, Xingxing Wang, Yoshiteru Murofushi, Miho M Suzuki, Hiroo Koyama, Yutaka Kondo

{"title":"Novel pharmacologic inhibition of lysine-specific demethylase 1 as a potential therapeutic for glioblastoma.","authors":"Keiko Shinjo, Takashi Umehara, Hideaki Niwa, Shin Sato, Keisuke Katsushima, Shinya Sato, Xingxing Wang, Yoshiteru Murofushi, Miho M Suzuki, Hiroo Koyama, Yutaka Kondo","doi":"10.1038/s41417-024-00847-8","DOIUrl":"https://doi.org/10.1038/s41417-024-00847-8","url":null,"abstract":"Lysine-specific demethylase 1 (LSD1/KDM1A) is a pivotal epigenetic enzyme that contributes to several malignancies including malignant glioma. LSD1 is a flavin adenine dinucleotide dependent histone demethylase that specifically targets histone H3 lysine (K) 4 mono- (me1) and di-methylation (me2) and H3K9me1/2 for demethylation. Herein we report the development of an LSD inhibitor, S2172, which efficiently penetrates the blood-brain barrier. S2172 effectively suppresses LSD1 enzymatic activity, resulting in the depletion of cell growth both in vitro in glioma stem cells (GSCs) (mean half-maximal inhibitory concentration (IC50) of 13.8 μM) and in vivo in a GSC orthotopic xenograft mouse model. Treatment with S2172 robustly reduced the expression of the stemness-related genes MYC and Nestin in GSC cells. Consistent with this, chromatin immunoprecipitation-sequencing revealed a significant S2172-dependent alteration in H3K4me2/H3K4me3 status. Furthermore, we identified 284 newly acquired H3K4me2 peak regions after S2172 treatment, which were encompassed within super-enhancer regions. The altered H3K4me2/H3K4me3 status induced by S2172 treatment affected the expression of genes related to tumorigenesis. Our data suggest that targeting LSD1 with S2172 could provide a promising treatment option for glioblastomas, particularly due to targeting of GSC populations.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

BAIAP2L2 promotes the malignancy of hepatocellular carcinoma via GABPB1-mediated reactive oxygen species imbalance. BAIAP2L2 通过 GABPB1 介导的活性氧失衡促进肝细胞癌的恶性发展。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-11-04 DOI: 10.1038/s41417-024-00841-0

Wenbo Jia, Bin Xu, Liang Yu, Yanzhi Feng, Jinyi Wang, Chao Xu, Litao Liang, Yongping Zhou, Wenzhou Ding, Lianbao Kong

引用次数: 0

Role of non-coding RNA in lineage plasticity of prostate cancer. 非编码 RNA 在前列腺癌血统可塑性中的作用

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-11-04 DOI: 10.1038/s41417-024-00834-z

Wenhui Tan, Changkai Xiao, Min Ma, Youhan Cao, Zhenguo Huang, Xiaolan Wang, Ran Kang, Zhenfa Li, Ermao Li

{"title":"Role of non-coding RNA in lineage plasticity of prostate cancer.","authors":"Wenhui Tan, Changkai Xiao, Min Ma, Youhan Cao, Zhenguo Huang, Xiaolan Wang, Ran Kang, Zhenfa Li, Ermao Li","doi":"10.1038/s41417-024-00834-z","DOIUrl":"10.1038/s41417-024-00834-z","url":null,"abstract":"The treatment of prostate cancer (PCa) has made great progress in recent years, but treatment resistance always develops and can even lead to fatal disease. Exploring the mechanism of drug resistance is of great significance for improving treatment outcomes and developing biomarkers with predictive value. It is increasingly recognized that mechanism of drug resistance in advanced PCa is related to lineage plasticity and tissue differentiation. Specifically, one of the mechanisms by which castration-resistant prostate cancer (CRPC) cells acquire drug resistance and transform into neuroendocrine prostate cancer (NEPC) cells is lineage plasticity. NEPC is a subtype of PCa that is highly aggressive and lethal, with a median survival of only 7 months. With the development of high-throughput RNA sequencing technology, more and more non-coding RNAs have been identified, which play important roles in different diseases through different mechanisms. Several ncRNAs have shown great potential in PCa lineage plasticity and as biomarkers. In the review, the role of ncRNA in PCa lineage plasticity and its use as biomarkers were reviewed.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Baicalein inhibits cell proliferation and induces apoptosis in brain glioma cells by downregulating the LGR4-EGFR pathway. 黄芩素通过下调 LGR4-EGFR 通路抑制脑胶质瘤细胞增殖并诱导其凋亡。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-10-28 DOI: 10.1038/s41417-024-00825-0

Xiaobing Zhang, Xian Shao, Qingquan Bao, Lingyan He, Xuchen Qi

{"title":"Baicalein inhibits cell proliferation and induces apoptosis in brain glioma cells by downregulating the LGR4-EGFR pathway.","authors":"Xiaobing Zhang, Xian Shao, Qingquan Bao, Lingyan He, Xuchen Qi","doi":"10.1038/s41417-024-00825-0","DOIUrl":"https://doi.org/10.1038/s41417-024-00825-0","url":null,"abstract":"Patients diagnosed with brain glioma have a poor prognosis and limited therapeutic options. LGR4 is overexpressed in brain glioma and involved in the tumorigenesis of many tumors. Baicalein (BAI) is a kind of flavonoid that has exhibited anti-tumor effects in various tumors. Nevertheless, the functions and associations of BAI and LGR4 in brain glioma remain unclear. In this study, Gene Expression Profiling Interactive Analysis and Human Protein Atlas databases were used to perform expression and survival analysis of LGR4 in brain glioma patients. Subsequently, the significance of LGR4-EGFR in brain glioma cells (HS683 and KNS89) and brain glioma animal models was explored by RNA interference and subcutaneous transplantation. Additionally, brain glioma cells were treated with BAI to explore the roles and mechanisms of BAI in brain glioma. The results showed that LGR4 was highly expressed in brain glioma and was related to a poor prognosis. LGR4 knockdown repressed the proliferation and EGFR phosphorylation but induced apoptosis in brain glioma cells. However, these effects were reversed by EGFR overexpression and CBL knockdown. In contrast, both in vitro and in vivo experiments revealed that LGR4 overexpression facilitated brain glioma cell malignant behavior and promoted tumor development, but these effects were rescued by BAI and an EGFR inhibitor. Furthermore, si-LGR4 accelerated EGFR protein degradation, while oe-LGR4 exhibited the opposite effect. Without affecting normal cellular viability, BAI inhibited malignant behavior, interacted with LGR4, and blocked the LGR4-EGFR pathway for brain glioma cells. In conclusion, our data suggested that BAI inhibited brain glioma cell proliferation and induced apoptosis by downregulating the LGR4-EGFR pathway, which provides a novel strategy and potential therapeutic targets to treat brain glioma.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

SEMA7A-mediated juxtacrine stimulation of IGFBP-3 upregulates IL-17RB at pancreatic cancer invasive front. SEMA7A介导的IGFBP-3并体刺激可上调胰腺癌浸润前沿的IL-17RB。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-10-24 DOI: 10.1038/s41417-024-00849-6

Yi-Ing Chen, Sui-Chih Tien, Yi-Ling Ko, Chin-Chun Chang, Min-Fen Hsu, Hung Jen Chien, Hsuan-Yu Peng, Yung-Ming Jeng, Yun-Wen Tien, Yu-Ting Chang, Ming-Chu Chang, Chun-Mei Hu

{"title":"SEMA7A-mediated juxtacrine stimulation of IGFBP-3 upregulates IL-17RB at pancreatic cancer invasive front.","authors":"Yi-Ing Chen, Sui-Chih Tien, Yi-Ling Ko, Chin-Chun Chang, Min-Fen Hsu, Hung Jen Chien, Hsuan-Yu Peng, Yung-Ming Jeng, Yun-Wen Tien, Yu-Ting Chang, Ming-Chu Chang, Chun-Mei Hu","doi":"10.1038/s41417-024-00849-6","DOIUrl":"10.1038/s41417-024-00849-6","url":null,"abstract":"Tumor invasion is the hallmark of tumor malignancy. The invasive infiltration pattern of tumor cells located at the leading edge is highly correlated with metastasis and unfavorable patient outcomes. However, the regulatory mechanisms governing tumor malignancy at the invasive margin remain unclear. The IL-17B/IL-17RB pathway is known to promote pancreatic cancer invasion and metastasis, yet the specific mechanisms underlying IL-17RB upregulation during invasion are poorly understood. In this study, we unveiled a multistep process for IL-17RB upregulation at the invasive margin, which occurs through direct communication between tumor cells and fibroblasts. Tumor ATP1A1 facilitates plasma membrane expression of SEMA7A, which binds to and induces IGFBP-3 secretion from fibroblasts. The resulting gradient of IGFBP-3 influences the direction and enhances IL-17RB expression to regulate SNAI2 in invasion. These findings highlight the importance of local tumor-fibroblast interactions in promoting cancer cell invasiveness, potentially leading to the development of new therapeutic strategies targeting this communication.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0