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Long non-coding RNA PRSS23-AS1 as ceRNA promotes breast cancer progression by regulating EMT via miR-3176 /YBX1 axis

Cancer Gene Therapy volume 32, pages 1018–1029 (2025)Cite this article

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Abstract

Breast cancer (BC) remains a leading cause of cancer-related mortality, largely due to its aggressive proliferation and metastatic potential. Long non-coding RNAs (lncRNAs) have emerged as key regulators in tumor development and progression. This study explored the functional role and mechanism of Lnc-PRSS23-AS1 in BC. We assessed Lnc-PRSS23-AS1 expression and localization using fluorescence in situ hybridization, qRT-PCR, and Western blotting in BC tissues and cell lines. Binding interactions between Lnc-PRSS23-AS1, miR-3176, and Y-box binding protein 1 (YBX1) were validated through dual-luciferase reporter assays, RNA pulldown, and RNA immunoprecipitation. Lnc-PRSS23-AS1 was significantly upregulated in BC and predominantly localized in the cytoplasm. Silencing Lnc-PRSS23-AS1 or overexpressing miR-3176 suppressed BC cell proliferation, migration, and invasion in vitro and in vivo. Conversely, miR-3176 inhibition or YBX1 overexpression reversed these effects. Mechanistically, Lnc-PRSS23-AS1 promoted YBX1 protein expression by acting as a molecular sponge for miR-3176. These findings highlight the Lnc-PRSS23-AS1/miR-3176/YBX1 axis as a driver of BC progression and suggest Lnc-PRSS23-AS1 as a potential therapeutic target for breast cancer treatment.

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Fig. 1: Lnc-PRSS23-AS1 is highly expressed in BC cell lines and tissues.
Fig. 2: si-Lnc-PRSS23-AS1 affects BC cells progression, invasion, migration, and the expression of epithelial-mesenchymal transition (EMT) related proteins.
Fig. 3: Lnc-PRSS23-AS1 acts as a sponge of miR-3176 in BC.
Fig. 4: miR-3176 inhibits the progression, invasion, migration, and expression of EMT-related proteins in BC cells.
Fig. 5: miR-3176 directly binds to the 3’-UTR of YBX1 mRNA and suppresses YBX1 protein expression in BC cells.
Fig. 6: PcDNA3.1-YBX1 effectively counteracted the promotion of si-Lnc-PRSS23-AS1 or miR-3176 mimics on the invasion, migration, and the expression of EMT-related proteins in MCF7 cells.
Fig. 7: Suppressing miR-3176 expression attenuates the inhibition of si-Lnc-PRSS23-AS1 on BC progression in vivo.
Fig. 8

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References

  1. Harbeck N, Gnant M. Breast cancer. Lancet. 2017;389:1134–1150.

    Article  PubMed  Google Scholar 

  2. Xu H, Xu B. Breast cancer: epidemiology, risk factors and screening. Chin J Cancer Res. 2023;35:565–583.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Burstein HJ, Curigliano G, Thürlimann B, Weber WP, Poortmans P, Regan MM, et al. Customizing local and systemic therapies for women with early breast cancer: the St. Gallen International Consensus Guidelines for treatment of early breast cancer 2021. Ann Oncol. 2021;32:1216–1235.

    Article  CAS  PubMed  Google Scholar 

  4. Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023;73:17–48.

    PubMed  Google Scholar 

  5. Bi Z, Wang Y. Advances in regional nodal management of early-stage breast cancer. Chin J Cancer Res. 2024;36:215–225.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Castaneda M, den Hollander P, Kuburich NA, Rosen JM, Mani SA. Mechanisms of cancer metastasis. Semin Cancer Biol. 2022;87:17–31.

    Article  CAS  PubMed  Google Scholar 

  7. Fonseca VC, Sidiropoulou Z. Geriatric breast cancer: staging, molecular surrogates, and treatment. a review & meta-analysis. Aging Dis. 2024;15:1602–1618.

    PubMed  PubMed Central  Google Scholar 

  8. Schmitt AM, Chang HY. Long noncoding RNAs in cancer pathways. Cancer Cell. 2016;29:452–463.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Liu SJ, Dang HX, Lim DA, Feng FY, Maher CA. Long noncoding RNAs in cancer metastasis. Nat Rev Cancer. 2021;21:446–460.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Tang Y, Cheung BB, Atmadibrata B, Marshall GM, Dinger ME, Liu PY, et al. The regulatory role of long noncoding RNAs in cancer. Cancer Lett. 2017;391:12–19.

    Article  CAS  PubMed  Google Scholar 

  11. Winkle M, El-Daly SM, Fabbri M, Calin GA. Noncoding RNA therapeutics - challenges and potential solutions. Nat Rev Drug Discov. 2021;20:629–651.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Wei L, Sun J, Zhang N, Zheng Y, Wang X, Lv L, et al. Noncoding RNAs in gastric cancer: implications for drug resistance. Mol Cancer. 2020;19:62.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Wei L, Wang X, Lv L, Liu J, Xing H, Song Y, et al. The emerging role of microRNAs and long noncoding RNAs in drug resistance of hepatocellular carcinoma. Mol Cancer. 2019;18:147.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Zhang Y, Dong X, Guo X, Li C, Fan Y, Liu P, et al. LncRNA-BC069792 suppresses tumor progression by targeting KCNQ4 in breast cancer. Mol Cancer. 2023;22:41.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Jiang T, Zhu J, Jiang S, Chen Z, Xu P, Gong R, et al. Targeting lncRNA DDIT4-AS1 sensitizes triple negative breast cancer to chemotherapy via suppressing of autophagy. Adv Sci (Weinh). 2023;10:e2207257.

    Article  PubMed  Google Scholar 

  16. Meng Z, Zhang R, Wu X, Piao Z, Zhang M, Jin T. LncRNA HAGLROS promotes breast cancer evolution through miR-135b-3p/COL10A1 axis and exosome-mediated macrophage M2 polarization. Cell Death Dis. 2024;15:633.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Lin X, Zhuang S, Chen X, Du J, Zhong L, Ding J, et al. lncRNA ITGB8-AS1 functions as a ceRNA to promote colorectal cancer growth and migration through integrin-mediated focal adhesion signaling. Mol Ther. 2022;30:688–702.

    Article  CAS  PubMed  Google Scholar 

  18. Zhang Y, Luo M, Cui X, O’Connell D, Yang Y. Long noncoding RNA NEAT1 promotes ferroptosis by modulating the miR-362-3p/MIOX axis as a ceRNA. Cell Death Differ. 2022;29:1850–1863.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Xue ST, Zheng B, Cao SQ, Ding JC, Hu GS, Liu W, et al. Long non-coding RNA LINC00680 functions as a ceRNA to promote esophageal squamous cell carcinoma progression through the miR-423-5p/PAK6 axis. Mol Cancer. 2022;21:69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Wang X, Li X, Lin F, Sun H, Lin Y, Wang Z, et al. The lnc-CTSLP8 upregulates CTSL1 as a competitive endogenous RNA and promotes ovarian cancer metastasis. J Exp Clin Cancer Res. 2021;40:151.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Zhang X, Bian H, Wei W, Wang Q, Chen J, Hei R, et al. DLX5 promotes osteosarcoma progression via activation of the NOTCH signaling pathway. Am J Cancer Res. 2021;11:3354–74.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Zhang T, Deng L, Ji Y, Cheng G, Su D, Qiu B. Novel long noncoding RNA (lncRNA) panel as biomarkers for prognosis in lung squamous cell carcinoma via competitive endogenous RNA (ceRNA) network analysis. Transl Cancer Res. 2021;10:393–405.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Lyabin DN, Eliseeva IA, Ovchinnikov LP. YB-1 protein: functions and regulation. Wiley Interdiscip Rev RNA. 2014;5:95–110.

    Article  CAS  PubMed  Google Scholar 

  24. Zhang H, Yu H, Ren D, Sun Y, Guo F, Cai H, et al. CBX3 regulated By YBX1 promotes smoking-induced pancreatic cancer progression via inhibiting SMURF2 expression. Int J Biol Sci. 2022;18:3484–3497.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Evdokimova V, Tognon C, Ng T, Ruzanov P, Melnyk N, Fink D, et al. Translational activation of snail1 and other developmentally regulated transcription factors by YB-1 promotes an epithelial-mesenchymal transition. Cancer Cell. 2009;15:402–415.

    Article  CAS  PubMed  Google Scholar 

  26. Jayavelu AK, Schnöder TM, Perner F, Herzog C, Meiler A, Krishnamoorthy G, et al. Splicing factor YBX1 mediates persistence of JAK2-mutated neoplasms. Nature. 2020;588:157–163.

    Article  PubMed  Google Scholar 

  27. Zhang Y, Huang YX, Wang DL, Yang B, Yan HY, Lin LH, et al. LncRNA DSCAM-AS1 interacts with YBX1 to promote cancer progression by forming a positive feedback loop that activates FOXA1 transcription network. Theranostics. 2020;10:10823–10837.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Kong X, Li J, Li Y, Duan W, Qi Q, Wang T, et al. A novel long non-coding RNA AC073352.1 promotes metastasis and angiogenesis via interacting with YBX1 in breast cancer. Cell Death Dis. 2021;12:670.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Iyer MK, Niknafs YS, Malik R, Singhal U, Sahu A, Hosono Y, et al. The landscape of long noncoding RNAs in the human transcriptome. Nat Genet. 2015;47:199–208.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Bai Y, Gotz C, Chincarini G, Zhao Z, Slaney C, Boath J, et al. YBX1 integration of oncogenic PI3K/mTOR signalling regulates the fitness of malignant epithelial cells. Nat Commun. 2023;14:1591.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Huarte M. The emerging role of lncRNAs in cancer. Nat Med. 2015;21:1253–61.

    Article  CAS  PubMed  Google Scholar 

  32. Huang Z, Zhou JK, Peng Y, He W, Huang C. The role of long noncoding RNAs in hepatocellular carcinoma. Mol Cancer. 2020;19:77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Karreth FA, Pandolfi PP. ceRNA cross-talk in cancer: when ce-bling rivalries go awry. Cancer Discov. 2013;3:1113–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Lin J, Liao S, Liu Z, Li E, Wu X, Zeng W. LncRNA FGD5-AS1 accelerates cell proliferation in pancreatic cancer by regulating miR-520a-3p/KIAA1522 axis. Cancer Biol Ther. 2021;22:257–266.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Pan X, Chen S, Ye L, Xu S, Wang L, Sun Y. Long non-coding RNA DLGAP1-AS1 modulates the development of non-small-cell lung cancer via the microRNA-193a-5p/DTL axis. Lab Invest. 2022;102:1182–1191.

    Article  CAS  PubMed  Google Scholar 

  36. Berger AC, Korkut A, Kanchi RS, Hegde AM, Lenoir W, Liu W, et al. A comprehensive pan-cancer molecular study of gynecologic and breast cancers. Cancer Cell. 2018;33:690–705.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Ma W, Zhao F, Yu X, Guan S, Suo H, Tao Z, et al. Immune-related lncRNAs as predictors of survival in breast cancer: a prognostic signature. J Transl Med. 2020;18:442.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Chen LL. Linking long noncoding RNA localization and function. Trends Biochem Sci. 2016;41:761–72.

    Article  CAS  PubMed  Google Scholar 

  39. Statello L, Guo CJ, Chen LL, Huarte M. Gene regulation by long non-coding RNAs and its biological functions. Nat Rev Mol Cell Biol. 2021;22:96–118.

    Article  CAS  PubMed  Google Scholar 

  40. Tay Y, Rinn J, Pandolfi PP. The multilayered complexity of ceRNA crosstalk and competition. Nature. 2014;505:344–352.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Wu H, Liu B, Chen Z, Li G, Zhang Z. MSC-induced lncRNA HCP5 drove fatty acid oxidation through miR-3619-5p/AMPK/PGC1α/CEBPB axis to promote stemness and chemo-resistance of gastric cancer. Cell Death Dis. 2020;11:233.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Liu S, Chen W, Hu H, Zhang T, Wu T, Li X, et al. Long noncoding RNA PVT1 promotes breast cancer proliferation and metastasis by binding miR-128-3p and UPF1. Breast Cancer Res. 2021;23:115.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We would like to thank all laboratory members for their discussion of this manuscript.

Funding

No funding was received for this study.

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Author notes

  1. These authors contributed equally: Yun Huang, Mudan Feng, Yiwei Jiang.

Authors and Affiliations

  1. Department of General Surgery, The Sixth Medical Center, Chinese PLA General Hospital, Beijing, China

    Yun Huang, Yiwei Jiang, Mingkun Wang & Zhen Cao

  2. Department of Emergency, The Seventh Medical Centre, Chinese PLA General Hospital, Beijing, China

    Mudan Feng

  3. Department of General Surgery, School of Medicine, South China University of Technology, Guangzhou, China

    Yiwei Jiang & Zhen Cao

  4. Department of General Surgery, The First Medical Centre, Chinese PLA General Hospital, Beijing, China

    Maihuan Wang & Zhen Cao

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Contributions

HY and FM conducted the molecular biology analyses, participated in designing the study and collecting clinical specimens, and drafted the manuscript. WM, JY, and WM collected clinical specimens, participated in data analysis, and performed statistical analyses. CZ and WM conceived and designed the study, participated in data analysis and coordination, and assisted in drafting the manuscript. All authors have read and approved the final manuscript.

Corresponding authors

Correspondence to Mingkun Wang or Zhen Cao.

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The authors declare that they have no competing interests.

Ethics approval and consent to participate

The present study received approval from the Sixth Medical Center of the PLA General Hospital (Beijing, China) and adhered to the Declaration of Helsinki. All procedures involving animal care and use were approved by the Experimental Animal Ethics Committee of the Beijing Geneline Bioscience Biotechnology Company and followed the National Policy on the Use of Laboratory Animals.

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Huang, Y., Feng, M., Jiang, Y. et al. Long non-coding RNA PRSS23-AS1 as ceRNA promotes breast cancer progression by regulating EMT via miR-3176 /YBX1 axis. Cancer Gene Ther 32, 1018–1029 (2025). https://doi.org/10.1038/s41417-025-00943-3

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