Skip to main content
SpringerLink
Log in

LINC00467 mediates the 5-fluorouracil resistance in breast cancer cells

  • Published:
In Vitro Cellular & Developmental Biology - Animal Aims and scope Submit manuscript

Abstract

Breast cancer is a prevalent global disease that requires the development of effective therapeutic approaches. The occurrence of 5-fluorouracil (5-FU) resistance in breast cancer is emerging, which urgently needs new way to overcome the obstacle. In this study, we validated that the expression of LINC00467 is up-regulated in the breast cancer patients and breast cancer cells. In addition, the high expression of LINC00467 is associated with the 5-FU resistance of breast cancer cells. Interestingly, LINC00467 induced the homologous recombination (HR) repair via promoting the expression of NBS1 in 5-FU resistant breast cancer cells. Furthermore, miR-205 was validated as a common target of LINC00467 and NBS1, indicating that LINC00467 may induce NBS1 via the miRNA-mRNA target. Importantly, we identified that XBP1, as a transcription factor, induced the expression of LINC00467, which resulted in the enhanced HR efficiency and 5-FU resistance. Silencing XBP1 sensitized the 5-FU resistant breast cancer cells to the 5-FU treatment, whereas the ectopic expression of LINC00467 abrogated the effect of XBP1 silencing. In conclusion, LINC00467 enhances the 5-FU resistance by inducing NBS1-mediated DNA repair. LINC00467 also mediates the function of XBP1 in 5-FU resistance in breast cancer cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1.
Figure 2.
Figure 3.
Figure 4.
Figure 5.

Similar content being viewed by others

Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  • Abdel-Razeq H, Sharaf B (2022) Expanding the Clinical Use of CDK4/6 Inhibitors in the Treatment of Hormone Receptor-Positive, HER2-Negative Breast Cancer from Metastatic Setting to Adjuvant Setting. Drug Des Devel Ther 16:727–735

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Andruska ND, Zheng X, Yang X, Mao C, Cherian MM, Mahapatra L, Helferich WG, Shapiro DJ (2015) Estrogen receptor alpha inhibitor activates the unfolded protein response, blocks protein synthesis, and induces tumor regression. Proc Natl Acad Sci U S A 112:4737–4742

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  • Bian L, Meng Y, Zhang M, Li D (2019) MRE11-RAD50-NBS1 complex alterations and DNA damage response: implications for cancer treatment. Mol Cancer 18:169

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bouznad N, Rokavec M, Oner MG, Hermeking H (2023) miR-34a and IRE1A/XBP-1(S) Form a Double-Negative Feedback Loop to Regulate Hypoxia-Induced EMT, Metastasis, Chemo-Resistance and Autophagy. Cancers (Basel) 15(4):1143

  • Chen X, Luo Q, Xiao Y, Zhu J, Zhang Y, Ding J, Li J (2022) LINC00467: an oncogenic long noncoding RNA. Cancer Cell Int 22:303

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ding H, Luo Y, Hu K, Liu P, Xiong M (2019) LINC00467 promotes lung adenocarcinoma proliferation via sponging miR-20b-5p to activate CCND1 expression. Onco Targets Ther 12:6733–6743

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Deng LH, Zhao H, Bai LP, Xie J, Liu K, Yan F (2021) LINC00467 promotion of gastric cancer development by directly regulating miR-7-5p expression and downstream epidermal growth factor receptor. Bioengineered 12:9484–9495

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dubsky P, Pinker K, Cardoso F, Montagna G, Ritter M, Denkert C, Rubio IT, de Azambuja E, Curigliano G, Gentilini O, Gnant M, Gunthert A, Hauser N, Heil J, Knauer M, Knotek-Roggenbauerc M, Knox S, Kovacs T, Kuerer HM, Loibl S, Mannhart M, Meattini I, Penault-Llorca F, Radosevic-Robin N, Sager P, Spanic T, Steyerova P, Tausch C, Peeters M, Weber WP, Cardoso MJ, Poortmans P (2021) Breast conservation and axillary management after primary systemic therapy in patients with early-stage breast cancer: the Lucerne toolbox. Lancet Oncol 22:e18–e28

    Article  PubMed  Google Scholar 

  • English BC, Savage HP, Mahan SP, Diaz-Ochoa VE, Young BM, Abuaita BH, Sule G, Knight JS, O’Riordan MX, Baumler AJ, Tsolis RM (2023) The IRE1alpha-XBP1 Signaling Axis Promotes Glycolytic Reprogramming in Response to Inflammatory Stimuli. mBio 14:e0306822

    Article  PubMed  Google Scholar 

  • Li W, He Y, Chen W, Man W, Fu Q, Tan H, Guo H, Zhou J, Yang P (2021) Knockdown of LINC00467 contributed to Axitinib sensitivity in hepatocellular carcinoma through miR-509-3p/PDGFRA axis. Gene Ther 28:634–645

    Article  CAS  PubMed  Google Scholar 

  • Li Z, Liu J, Chen H, Zhang Y, Shi H, Huang L, Tao J, Shen R, Wang T (2020) Ferritin Light Chain (FTL) competes with long noncoding RNA LINC00467 for miR-133b binding site to regulate chemoresistance and metastasis of colorectal cancer. Carcinogenesis 41:467–477

    Article  CAS  PubMed  Google Scholar 

  • Liang R, Tang Y (2020) LINC00467 knockdown repressed cell proliferation but stimulated cell apoptosis in glioblastoma via miR-339-3p/IP6K2 axis. Cancer Biomark 28:169–180

    Article  CAS  PubMed  Google Scholar 

  • Mullen NJ, Singh PK (2023) Nucleotide metabolism: a pan-cancer metabolic dependency. Nat Rev Cancer 23:275–294

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Petrini JH (1999) The mammalian Mre11-Rad50-nbs1 protein complex: integration of functions in the cellular DNA-damage response. Am J Hum Genet 64:1264–1269

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shi J, Huang Y, Wen C, He S, Wu L, Zhou H (2020) Genome-wide identification and characterization of long non-coding RNAs involved in acquired resistance to gefitinib in non-small-cell lung cancer. Comput Biol Chem 87:107288

    Article  CAS  PubMed  Google Scholar 

  • Valencia-Lazcano AA, Hassan D, Pourmadadi M, Shamsabadipour A, Behzadmehr R, Rahdar A, Medina DI, Diez-Pascual AM (2023) 5-Fluorouracil nano-delivery systems as a cutting-edge for cancer therapy. Eur J Med Chem 246:114995

    Article  CAS  PubMed  Google Scholar 

  • Wu R, Zhang QH, Lu YJ, Ren K, Yi GH (2015) Involvement of the IRE1alpha-XBP1 pathway and XBP1s-dependent transcriptional reprogramming in metabolic diseases. DNA Cell Biol 34:6–18

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang Y, Zhang Y, Wang S, Cao B, Hu D, Jia J, Wang Y, Chen L, Li J, Liu H, Tang H (2022) LINC00467 facilitates the proliferation, migration and invasion of glioma via promoting the expression of inositol hexakisphosphate kinase 2 by binding to miR-339-3p. Bioengineered 13:3370–3382

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhu F, Liu Z, Zhou Q, Zhou D, Fan J, Bo H, Fan L (2023) Silencing of LINC00467 inhibits cell proliferation in testicular germ cell tumors cells. Biomol Biomed, https://doi.org/10.17305/bb.2023.8969

Download references

Author information

Authors and Affiliations

  1. Department of Oncology, the Affiliated Hospital of Southwest Medical University, Taping Rd. No.25, Luzhou, China

    Lan Li, Yan Zhang, Yuwei Zhan, Yuanke Zhong & Xuehong Li

Authors
  1. Lan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yan Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yuwei Zhan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yuanke Zhong
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xuehong Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by L.L, Y.Z, Y.Z and Y.Z. X.L supervised the study. The first draft of the manuscript was written by L.L and X.L, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Xuehong Li.

Ethics declarations

Conflicts of interest/Competing interests

The authors declare that they have no conflict of interest.

Ethics approval

The breast cancer tumor sample collection and experiments were approved by the Institutional Ethical Committee of Southwest Medical University with the issue number No. SMU19028.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, L., Zhang, Y., Zhan, Y. et al. LINC00467 mediates the 5-fluorouracil resistance in breast cancer cells. In Vitro Cell.Dev.Biol.-Animal 60, 80–88 (2024). https://doi.org/10.1007/s11626-023-00832-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11626-023-00832-9

Keywords

Search

Navigation