Abstract

Abstract The human genome expresses a large number of long non-coding RNAs (lncRNAs), however, little is known about their physiological functions or their role in cancer for the vast majority of these lncRNAs. In the present study, we identified a set of lncRNAs that were differentially expressed in breast cancer tissues as compared to normal tissue. Among them is AK023948 which is up-regulated in breast cancer tissue and in breast cancer cell lines. Ectopic expression of AK023948 in breast cancer MCF-7 cells promotes proliferation and anchorage independent cell growth along with activation of AKT phosphorylation. On the other hand, knockdown or knockout of AK023948 in MCF-7 cells reduces the proliferation of cells and phosphorylation of AKT. Furthermore, there is a positive correlation between AK023948 and pAKT expression in breast cancer tissue microarray. To determine the underlying mechanism of AK023948-mediated activation of AKT, we performed RNA precipitation assays using biotin-labeled AK023948 RNA probe, followed by PAGE analysis, and detected a unique protein band by silver staining. Mass spectrometry analysis identified it as ATP dependent RNA helicase A (RHA/DHX9) which was confirmed by Western blot and RNA immunoprecipitation (IP), respectively. Co-IP indicated that DHX9 interacts with p85PI3K regulatory subunit. Further characterization revealed that p85-DHX9 interaction is essential for stability of p85α and AKT phosphorylation. Together, these results suggest that AK023948 may function as an oncogenic lncRNA in breast cancer and thus, it may serve as a novel target for breast cancer therapy. Citation Format: Pratirodh Koirala, Yin Yuan MO. LncRNA AK023948 promotes breast tumorigenesis by enhancing AKT phosphorylation. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 155. doi:10.1158/1538-7445.AM2015-155

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