Abstract
Abstract Trastuzumab is an effective treatment for HER2+ breast cancer. However, trastuzumab resistance in HER2+ breast cancer may induce the epithelial-to-mesenchymal transition (EMT), transforming HER2+ to triple-negative breast cancer with cancer stem cell properties in some cancer cell populations. Long noncoding RNAs (lncRNAs) have been reported to be upregulated in many types of cancer tissues, and might play significant regulatory roles in cancer progression. However, the mechanisms of lncRNA in trastuzumab resistance still remain largely unknown. Here, we systematically analyzed the levels of LincRNA between BT474 (HER2+trastuzumab-sensitive) and the PTEN-deficient trastuzumab-resistant derivative (BT474-PTEN-LTT) by using RNA-sequencing, and identified that Linc00162 was significantly overexpressed in BT474 PTEN- LTT cells. In vitro functional assay indicated that downregulation of Linc00162 in BT474 PTEN-LTT cells completely inhibited the cell proliferation. To further evaluate the role of Linc00162 in BCSC self-renewal, we found that inhibition of Linc00162 led to a significant reduction in the number and the size of LTT cells sphere by using the mammosphere formation assay. Next, we examined Linc00162 expression levels in breast cancer tissues, and identified that Linc00162 was markedly increased. Clinicopathologic relevance analysis showed that Linc00162 expression was correlated with advanced clinical stage, lymph node metastasis and the depth of invasion. Furthermore, upregulation of Linc00162 was correlated with TRNB phenotype. In Kaplan-Meier survival analysis, high levels of Linc00162 was significantly associated with unfavorable survival in breast cancer patients. These findings suggest that Linc00162 can be used as a clinically relevant novel biomarker in breast cancer and may serve as a target for future drug development. Citation Format: Lichao Sun, ChangChing Lin, Joseph Burnett, Hebao Yuan, Duxin Sun. Long noncoding RNA Linc00162, as a novel prognostic marker, modulates cancer stem cell properties in triple-negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4604.
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