Evidence map›Paper›PMID 40118782›Full record

ArticleClinical and translational medicine2025

HIF-1α-induced long noncoding RNA LINC02776 promotes drug resistance of ovarian cancer by increasing polyADP-ribosylation.

Yangjun Wu, Yu Zeng, Yong Wu, Xinyu Ha, Zheng Feng, Chaohua Liu, Ziqi Liu, Jiajia Wang, Xingzhu Ju, Shenglin Huang and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical and translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

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0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

17 authors.

Yangjun WuDepartment of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.
Yu ZengPrecision Research Center for Refractory Diseases and Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yong WuDepartment of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.
Xinyu HaDepartment of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.
Zheng FengDepartment of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.
Chaohua LiuDepartment of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.
Ziqi LiuDepartment of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.
Jiajia WangDepartment of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.
Xingzhu JuDepartment of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.
Shenglin HuangKey Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.
Linhui LiangKey Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.
Bin ZhengAccurate International Biotechnology Co. Ltd., Guangzhou, China.
Lulu YangWuhan Benagen Technology Co., Ltd, Wuhan, China.
Jun WangWuhan Benagen Technology Co., Ltd, Wuhan, China.
Xiaohua WuDepartment of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.
Shengli LiPrecision Research Center for Refractory Diseases and Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.ORCID 0000-0001-5430-303X
Hao WenDepartment of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.

Funding

Chinese Society of Clinical Oncology Y-2019AMZS-0468Hubei Province Key Research and Development Project 2022BCA022National Natural Science Foundation of China 82204029National Natural Science Foundation of China 82272898Shanghai Rising-Star Program 23QA1407800
6 · The paper itself

Abstract

backgroundChemoresistance remains a major hurdle in ovarian cancer (OC) treatment, as many patients eventually develop resistance to platinum-based chemotherapy and/or PARP inhibitors (PARPi).

methodsWe performed transcriptome-wide analysis by RNA sequencing (RNA-seq) data of platinum-resistant and -sensitive OC tissues. We demonstrated the role of LINC02776 in platinum resistance in OC cells, mice models and patient-derived organoid (PDO) models.

resultsWe identify the long noncoding RNA LINC02776 as a critical factor of platinum resistance. Elevated expression of LINC02776 is observed in platinum-resistant OC and serves as an independent prognostic factor for OC patients. Functionally, silencing LINC02776 reduces proliferation and DNA damage repair in OC cells, thereby enhancing sensitivity to platinum and PARPi in both xenograft mouse models and patient-derived organoid (PDO) models with acquired chemoresistance. Mechanistically, LINC02776 binds to the catalytic domain of poly (ADP-ribose) polymerase 1 (PARP1), promoting PARP1-dependent polyADP-ribosylation (PARylation) and facilitating homologous recombination (HR) restoration. Additionally, high HIF-1α expression in platinum-resistant tissues further stimulates LINC02776 transcription.

conclusionsOur findings suggest that targeting LINC02776 represents a promising therapeutic strategy for OC patients who have developed resistance to platinum or PARPi. KEY POINTS: LINC02776 promotes OC cell proliferation by regulating DNA damage and apoptosis signaling pathways. LINC02776 binds PARP1 to promote DNA damage-triggered PARylation in OC cells. LINC02776 mediates cisplatin and olaparib resistance in OC cells by enhancing PARP1-mediated PARylation activity and regulating the PARP1-mediated HR pathway. The high expression of LINC02776 is induced by HIF-1α in platinum-resistant OC cells and tissues.

Indexed as

Drug Resistance, NeoplasmHypoxia-Inducible Factor 1, alpha SubunitOvarian NeoplasmsPoly ADP RibosylationRNA, Long NoncodingAnimalsCell Line, TumorFemaleHumansMicePoly (ADP-Ribose) Polymerase-1HIF1A protein, humanHypoxia-Inducible Factor 1, alpha SubunitPoly (ADP-Ribose) Polymerase-1RNA, Long NoncodingHIF‐1αLINC02776ovarian cancerPARP1PARPi resistanceplatinum resistance

Identifiers

PMID40118782
PMCPMC11928293

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.