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ARTICLE

Multi-Scale Transcriptomic Sequencing Data Analysis Reveals LINC00467 is Associated with Malignant Progression in Breast Cancer: An In Silico and In Vitro Study

Hui Zha1,#, Chao Li2,#, Jia Chen3, Hao Bo2, Zhaolan Hu4, Zailong Qin5,6,*, Jie Guo7,8,*, Junbin Yuan1,*
1 Department of Urology, Xiangya Hospital, Central South University, Changsha, China
2 NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, Institute of Reproductive and Stem Cell Engineering, Central South University, Changsha, China
3 Department of Plastic Surgery, The Third Xiangya Hospital, Central South University, Changsha, China
4 Department of Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha, China
5 Guangxi Key Laboratory of Reproductive Health and Birth Defect Prevention, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
6 Genetic and Metabolic Central Laboratory, Birth Defects Prevention and Control Institute of Guangxi Zhuang Autonomous Region, Nanning, China
7 National Institute of Drug Clinical Trial, Xiangya Hospital, Central South University, Changsha, China
8 China National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
* Corresponding Author: Zailong Qin. Email: email; Jie Guo. Email: email; Junbin Yuan. Email: email
# These authors contributed equally to this work
(This article belongs to the Special Issue: Breast Cancer Biomarkers and Drug Targets Discoveries Towards a More Personalized Treatment Setting)

Oncology Research https://doi.org/10.32604/or.2026.067601

Received 07 May 2025; Accepted 26 December 2025; Published online 18 February 2026

Abstract

Objective: Long non-coding RNAs have been found to play a pivotal role in breast cancer, yet the majority of these lncRNAs remain to be thoroughly investigated. This study aimed to explore the role of differentially expressed long non-coding RNAs (lncRNAs) in breast cancer stemness and drug sensitivity. Methods: Database mining was performed to evaluate the expression of LINC00467 in different types of breast cancer and its association with clinical features. The function of LINC00467 was examined through colony formation assays, quantitative reverse transcription PCR (qRT-PCR), and western blotting following LINC00467 silencing in breast cancer cell lines. Results: LINC00467 was significantly upregulated in various breast cancer subtypes with spatial specificity. Silencing LINC00467 reduced clonogenic capacity and downregulated the stemness-associated factor LIN28B as well as phosphorylated RAC-alpha serine/threonine-protein kinase (p-AKT). The transcription factors specificity protein 1 (SP1) and E2F transcription factor 1 (E2F1) were predicted to bind to the LINC00467 promoter. Furthermore, breast cancer samples with high LINC00467 expression displayed reduced sensitivity to AKT inhibitors, and high LINC00467 expression was negatively correlated with the therapeutic response to programmed cell death 1 (PD-1) antibodies. Conclusion: Our findings suggest that spatially expressed LINC00467 may promote breast cancer stemness by regulating AKT signaling and could serve as a potential new therapeutic target and indicator of drug sensitivity in breast cancer.

Keywords

Breast cancer; LINC00467; cell stemness; single cell sequencing; drug sensitivity

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