Abstract
Breast cancer is one of the major malignant tumors among women worldwide. Long noncoding RNAs (lncRNAs) have been documented as significant modulators in the development and progression of various cancers; however, the contribution of lncRNAs to breast cancer remains largely unknown. In this study, we found a novel lncRNA (NONHSAT137675) whose expression was significantly increased in the breast cancer tissues. We named the novel lncRNA as lncRNA PRBC (PABPC1-related lncRNA in breast cancer) and identified it as a key lncRNA associated with breast cancer progression and prognosis. Functional analysis displayed that lncRNA PRBC could promote autophagy and progression of breast cancer. Mechanistically, we verified that lncRNA PRBC physically interacted with PABPC1 through RIP assay, and PABPC1 overexpression could reverse the inhibiting effect of lncRNA PRBC knockdown on the malignant behaviors in breast cancer cells. Knockdown of lncRNA PRBC interfered the translocation of PABPC1 from nucleus to cytoplasm as indicated by western blot and IF assays. Significantly, the cytoplasmic location of PABPC1 was required for the interaction between PABPC1 and AGO2, which could be enhanced by lncRNA PRBC overexpression, leading to strengthened recruitment of mRNA to RNA-induced silencing complex (RISC) and thus reinforcing the inhibition efficiency of miRNAs. In general, lncRNA PRBC played a critical role in malignant progression of breast cancer by inducing the cytoplasmic translocation of PABPC1 to further regulate the function of downstream miRNAs. This study provides novel insight on the molecular mechanism of breast cancer progression, and lncRNA PRBC might be a promising therapeutic target and prognostic predictor for breast cancer.
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The data in this study are available from the corresponding author upon reasonable request.
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Acknowledgements
This work was supported by Special Foundation for Taishan Scholars (No. ts20190971), Special Support Plan for National High Level Talents (Ten Thousand Talents Program W01020103), Foundation from Clinical Research Center of Shandong University (No.2020SDUCRCA015), Qilu Hospital Clinical New Technology Developing Foundation (No. 2019-3).
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YL, BC, PS and QY conceived the study. FX, LL, YW, DL, FY, YL, YJ and LW helped to perform the experiments. YL, BC, WZ and LW analyzed the data. XK and PS collected clinical samples. YL, BC, PS and QY wrote and revised the paper. All authors have read and approved the final manuscript.
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Liang, Y., Chen, B., Xu, F. et al. LncRNA PRBC induces autophagy to promote breast cancer progression through modulating PABPC1-mediated mRNA stabilization. Oncogene 43, 1019–1032 (2024). https://doi.org/10.1038/s41388-024-02971-z
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DOI: https://doi.org/10.1038/s41388-024-02971-z