Xiao Li, Zhen Zheng, Wanzhen Zhou, Huixian Huang, Yang Zhou, Qinyang Xu, Xiaolu Zhu, Yincheng Teng
{"title":"HOXB2通过上调lncRNA DANCR促进卵巢癌的顺铂耐药性","authors":"Xiao Li, Zhen Zheng, Wanzhen Zhou, Huixian Huang, Yang Zhou, Qinyang Xu, Xiaolu Zhu, Yincheng Teng","doi":"10.1186/s13048-024-01424-1","DOIUrl":null,"url":null,"abstract":"<p><p>Ovarian cancer (OV) is a highly fatal malignant disease that commonly manifests at an advanced stage. Drug resistance, particularly platinum resistance, is a leading cause of treatment failure because first-line systemic chemotherapy primarily relies on platinum-based regimens. By analyzing the gene expression levels in the Cancer Genome Atlas database, Genotype-Tissue Expression database, and Gene Expression Omnibus datasets, we discerned that HOXB2 was highly expressed in OV and was associated with poor prognosis and cisplatin resistance. Immunohistochemistry and loss-of-function experiments on HOXB2 were conducted to explore its role in OV. We observed that suppressing HOXB2 could impair the growth and cisplatin resistance of OV in vivo and in vitro. Mechanical investigation and experimental validation based on RNA-Seq revealed that HOXB2 regulated ATP-binding cassette transporter members and the ERK signaling pathway. We further demonstrated that HOXB2 modulated the expression of long non-coding RNA DANCR, a differentiation antagonizing non-protein coding RNA, and thus influenced its downstream effectors ABCA1, ABCG1, and ERK signaling to boost drug resistance and cancer proliferation. These results verified that high expression of HOXB2 correlated with platinum resistance and poor prognosis of OV. Therefore, targeting HOXB2 may be a promising strategy for OV therapy.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":null,"pages":null},"PeriodicalIF":3.8000,"publicationDate":"2024-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11161928/pdf/","citationCount":"0","resultStr":"{\"title\":\"HOXB2 promotes cisplatin resistance by upregulating lncRNA DANCR in ovarian cancer.\",\"authors\":\"Xiao Li, Zhen Zheng, Wanzhen Zhou, Huixian Huang, Yang Zhou, Qinyang Xu, Xiaolu Zhu, Yincheng Teng\",\"doi\":\"10.1186/s13048-024-01424-1\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Ovarian cancer (OV) is a highly fatal malignant disease that commonly manifests at an advanced stage. Drug resistance, particularly platinum resistance, is a leading cause of treatment failure because first-line systemic chemotherapy primarily relies on platinum-based regimens. By analyzing the gene expression levels in the Cancer Genome Atlas database, Genotype-Tissue Expression database, and Gene Expression Omnibus datasets, we discerned that HOXB2 was highly expressed in OV and was associated with poor prognosis and cisplatin resistance. Immunohistochemistry and loss-of-function experiments on HOXB2 were conducted to explore its role in OV. We observed that suppressing HOXB2 could impair the growth and cisplatin resistance of OV in vivo and in vitro. Mechanical investigation and experimental validation based on RNA-Seq revealed that HOXB2 regulated ATP-binding cassette transporter members and the ERK signaling pathway. We further demonstrated that HOXB2 modulated the expression of long non-coding RNA DANCR, a differentiation antagonizing non-protein coding RNA, and thus influenced its downstream effectors ABCA1, ABCG1, and ERK signaling to boost drug resistance and cancer proliferation. These results verified that high expression of HOXB2 correlated with platinum resistance and poor prognosis of OV. Therefore, targeting HOXB2 may be a promising strategy for OV therapy.</p>\",\"PeriodicalId\":16610,\"journal\":{\"name\":\"Journal of Ovarian Research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.8000,\"publicationDate\":\"2024-06-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11161928/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Ovarian Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s13048-024-01424-1\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"REPRODUCTIVE BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Ovarian Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13048-024-01424-1","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"REPRODUCTIVE BIOLOGY","Score":null,"Total":0}
HOXB2 promotes cisplatin resistance by upregulating lncRNA DANCR in ovarian cancer.
Ovarian cancer (OV) is a highly fatal malignant disease that commonly manifests at an advanced stage. Drug resistance, particularly platinum resistance, is a leading cause of treatment failure because first-line systemic chemotherapy primarily relies on platinum-based regimens. By analyzing the gene expression levels in the Cancer Genome Atlas database, Genotype-Tissue Expression database, and Gene Expression Omnibus datasets, we discerned that HOXB2 was highly expressed in OV and was associated with poor prognosis and cisplatin resistance. Immunohistochemistry and loss-of-function experiments on HOXB2 were conducted to explore its role in OV. We observed that suppressing HOXB2 could impair the growth and cisplatin resistance of OV in vivo and in vitro. Mechanical investigation and experimental validation based on RNA-Seq revealed that HOXB2 regulated ATP-binding cassette transporter members and the ERK signaling pathway. We further demonstrated that HOXB2 modulated the expression of long non-coding RNA DANCR, a differentiation antagonizing non-protein coding RNA, and thus influenced its downstream effectors ABCA1, ABCG1, and ERK signaling to boost drug resistance and cancer proliferation. These results verified that high expression of HOXB2 correlated with platinum resistance and poor prognosis of OV. Therefore, targeting HOXB2 may be a promising strategy for OV therapy.
期刊介绍:
Journal of Ovarian Research is an open access, peer reviewed, online journal that aims to provide a forum for high-quality basic and clinical research on ovarian function, abnormalities, and cancer. The journal focuses on research that provides new insights into ovarian functions as well as prevention and treatment of diseases afflicting the organ.
Topical areas include, but are not restricted to:
Ovary development, hormone secretion and regulation
Follicle growth and ovulation
Infertility and Polycystic ovarian syndrome
Regulation of pituitary and other biological functions by ovarian hormones
Ovarian cancer, its prevention, diagnosis and treatment
Drug development and screening
Role of stem cells in ovary development and function.