Hui Li, Yanyan Sun, Jue Wang, Zhiwu Wang, Lan Wu, Jie Lei, Ying Gao
{"title":"携带ZNF516的透明质酸修饰的乳外泌体抑制ABCC5并有助于肺腺癌培美曲塞的敏感性。","authors":"Hui Li, Yanyan Sun, Jue Wang, Zhiwu Wang, Lan Wu, Jie Lei, Ying Gao","doi":"10.1007/s13577-025-01219-6","DOIUrl":null,"url":null,"abstract":"<p><p>Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer. Milk-derived exosomes (mEXOs) have critical roles in cancer treatment. This paper explores the effects of hyaluronic acid (HA)-modified mEXOs (HA-mEXOs) in LUAD. HA-mEXOs were isolated and prepared, and PMX-resistant cells were developed. CCK-8, colony formation, Transwell, flow apoptosis, xenograft tumor assay, immunohistochemistry, and TUNEL experiments were conducted to explore the impact of mEXOs and HA-mEXOs on malignant behaviors and PMX sensitivity. The role of ZNF516 and ABCC5 on malignant behaviors and PMX sensitivity was investigated by shRNA lentiviral infection. HA modification increased the uptake and affinity of LUAD cells for mEXOs. mEXOs induced PMX-resistant LUAD cell sensitivity and inhibited their malignant behaviors. mEXOs enhanced PMX sensitivity and inhibited tumor growth. HA-mEXOs had superior effects to mEXOs. ZNF516 was lowered in LUAD-resistant cells and upregulated by mEXOs. ZNF516 bound to the ABCC5 promoter and repressed its transcriptional activation. The combined knockdown of ZNF516 reversed the antitumor benefits of mEXOs. HA-mEXOs-carrying ZNF516 enhance ZNF516 levels in LUAD/PMX cells and repress ABCC5, which in turn induces cell sensitivity to PMX and inhibits LUAD progression.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 3","pages":"92"},"PeriodicalIF":3.4000,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Hyaluronic acid-modified milk exosomes carrying ZNF516 inhibit ABCC5 and contribute to pemetrexed sensitivity in lung adenocarcinoma.\",\"authors\":\"Hui Li, Yanyan Sun, Jue Wang, Zhiwu Wang, Lan Wu, Jie Lei, Ying Gao\",\"doi\":\"10.1007/s13577-025-01219-6\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer. Milk-derived exosomes (mEXOs) have critical roles in cancer treatment. This paper explores the effects of hyaluronic acid (HA)-modified mEXOs (HA-mEXOs) in LUAD. HA-mEXOs were isolated and prepared, and PMX-resistant cells were developed. CCK-8, colony formation, Transwell, flow apoptosis, xenograft tumor assay, immunohistochemistry, and TUNEL experiments were conducted to explore the impact of mEXOs and HA-mEXOs on malignant behaviors and PMX sensitivity. The role of ZNF516 and ABCC5 on malignant behaviors and PMX sensitivity was investigated by shRNA lentiviral infection. HA modification increased the uptake and affinity of LUAD cells for mEXOs. mEXOs induced PMX-resistant LUAD cell sensitivity and inhibited their malignant behaviors. mEXOs enhanced PMX sensitivity and inhibited tumor growth. HA-mEXOs had superior effects to mEXOs. ZNF516 was lowered in LUAD-resistant cells and upregulated by mEXOs. ZNF516 bound to the ABCC5 promoter and repressed its transcriptional activation. The combined knockdown of ZNF516 reversed the antitumor benefits of mEXOs. HA-mEXOs-carrying ZNF516 enhance ZNF516 levels in LUAD/PMX cells and repress ABCC5, which in turn induces cell sensitivity to PMX and inhibits LUAD progression.</p>\",\"PeriodicalId\":49194,\"journal\":{\"name\":\"Human Cell\",\"volume\":\"38 3\",\"pages\":\"92\"},\"PeriodicalIF\":3.4000,\"publicationDate\":\"2025-04-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Human Cell\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1007/s13577-025-01219-6\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Human Cell","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1007/s13577-025-01219-6","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
Hyaluronic acid-modified milk exosomes carrying ZNF516 inhibit ABCC5 and contribute to pemetrexed sensitivity in lung adenocarcinoma.
Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer. Milk-derived exosomes (mEXOs) have critical roles in cancer treatment. This paper explores the effects of hyaluronic acid (HA)-modified mEXOs (HA-mEXOs) in LUAD. HA-mEXOs were isolated and prepared, and PMX-resistant cells were developed. CCK-8, colony formation, Transwell, flow apoptosis, xenograft tumor assay, immunohistochemistry, and TUNEL experiments were conducted to explore the impact of mEXOs and HA-mEXOs on malignant behaviors and PMX sensitivity. The role of ZNF516 and ABCC5 on malignant behaviors and PMX sensitivity was investigated by shRNA lentiviral infection. HA modification increased the uptake and affinity of LUAD cells for mEXOs. mEXOs induced PMX-resistant LUAD cell sensitivity and inhibited their malignant behaviors. mEXOs enhanced PMX sensitivity and inhibited tumor growth. HA-mEXOs had superior effects to mEXOs. ZNF516 was lowered in LUAD-resistant cells and upregulated by mEXOs. ZNF516 bound to the ABCC5 promoter and repressed its transcriptional activation. The combined knockdown of ZNF516 reversed the antitumor benefits of mEXOs. HA-mEXOs-carrying ZNF516 enhance ZNF516 levels in LUAD/PMX cells and repress ABCC5, which in turn induces cell sensitivity to PMX and inhibits LUAD progression.
期刊介绍：
Human Cell is the official English-language journal of the Japan Human Cell Society. The journal serves as a forum for international research on all aspects of the human cell, encompassing not only cell biology but also pathology, cytology, and oncology, including clinical oncology. Embryonic stem cells derived from animals, regenerative medicine using animal cells, and experimental animal models with implications for human diseases are covered as well.
Submissions in any of the following categories will be considered: Research Articles, Cell Lines, Rapid Communications, Reviews, and Letters to the Editor. A brief clinical case report focusing on cellular responses to pathological insults in human studies may also be submitted as a Letter to the Editor in a concise and short format.
Not only basic scientists but also gynecologists, oncologists, and other clinical scientists are welcome to submit work expressing new ideas or research using human cells.
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