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bioRxiv · 10.1101/2022.09.06.506751

lncRNA-WAL Promotes Aggressiveness of Triple-Negative Breast Cancer via inducing β-Catenin nuclear translocation.

Huang, H.·Jin, H.·Lei, R.·He, Z.·He, S.·Chen, J.·Saw, P.·Qiu, Z.·Ren, G.·Nie, Y.
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Abstract

Because of its insensitive to existing radiotherapy, chemotherapy and targeted treatments, Triple-negative breast cancer (TNBC) remains a great challenge to overcome. More and more evidence has indicated abnormal wnt/{beta}-catenin pathway activation in TNBC but not luminal or her2+ breast cancer, and lncRNAs play a key role in a variety of cancers. Through lncRNA microarray profiling between Activated and inactivated Wnt/{beta}-catenin pathway of TNBC tissues, lnc-WAL (Wnt/{beta}-catenin associated lncRNA; WAL) was selected as the top up-regulated lncRNA in Wnt/{beta}-catenin pathway activation compared with the inactivation group. RIP-seq was analyzed between {beta}-catenin and IgG groups of, where lnc-WAL could interact with {beta}-catenin. Clinically, increased lnc-WAL in the TNBC tumor tissue was associated with shorter survival. lnc-WAL promoted the EMT, the ability of breast cancer stem cells (BCSC), proliferation, migration and invasion of TNBC cells. Mechanistically, lnc-WAL inhibited {beta}-catenin protein degradation via Axin-mediated phosphorylation at serine 45. Subsequently, {beta}-catenin was accumulated in nuclear and activated the target genes. Importantly, Wnt/{beta}-catenin pathway activation stimulated the transcription of lnc-WAL. These results pointed to a master regulatory role of lnc-WAL/Axin/{beta}-catenin in the malignant progression of TNBC. Our findings provide important clinical translational evidence that lnc-WAL maybe as potential therapeutic target against TNBC.

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Huang, H., Jin, H., Lei, R., He, Z., He, S., Chen, J., Saw, P., Qiu, Z., Ren, G., Nie, Y.. 2022-09-07. lncRNA-WAL Promotes Aggressiveness of Triple-Negative Breast Cancer via inducing β-Catenin nuclear translocation.. https://doi.org/10.1101/2022.09.06.506751

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