Abstract
Abstract The prognosis of breast cancer patients with metastasis is still poor even improved by current treatment modalities. Unveiling new biomarkers and molecular mechanisms that underlie metastasis are of vital importance for the treatment of breast cancer. The recent discovery of long noncoding RNAs (lncRNAs) has gained widespread attention. To identify critical lncRNAs that contributed to breast cancer metastasis, we profiled their expression in 5 pairs of primary tumors and lymph nodes metastasis loci by HTA2.0 microarray. LINC02273 is significantly upregulated in metastasis loci and its high expression is associated with poor diseases free survival in a validation set of 254 patients. LINC02273 was mainly located in the cell nucleus . RACE-PCR showed two isoforms and the longest one was the most abundant isoform in breast cancer. Through transwell assay, 3D spheroid invasion assay and mice xenograft metastasis model, we found that LINC02273 promoted breast cancer cell migration, invasion and metastasis. Via mass spectrometry, hnRNPL was found to interact with LINC02273 to enhance its stability, which was further confirmed by Actinomycin D inhibition assay and luciferase reporter assay. Furthermore, ChIRP-seq and ChIP-seq showed that LINC02273 stimulated oncogene AGR2 expression by directly binding to the AGR2 promoter region and increasing H3K27ac modification. Triplex formation assay was performed for verification. We demonstrated that the expression level and oncogenic ability of AGR2 were regulated by hnRNPL through LINC02273. Clinical data and mouse xenograft tumors also revealed the positive correlation of AGR2 and LINC02273. In conclusion, LINC02273, which is stabilized by hnRNPL can promote breast cancer metastasis through upregulation of AGR2 and may serve as a prognostic biomarker for breast cancer. Citation Format: Xiu B, Chi Y, Ji W, Zhang Q, Wu J. LINC02273 interacts with hnRNPL and promotes metastasis through directly activating AGR2 in breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-05-08.
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