Abstract 3579: Long non-coding RNA ADAMTS9-AS2 inhibits ovarian tumor growth via Annexin A1

Abstract

Non-coding RNAs (ncRNA), which account for more than 75% genome transcripts, have unique functions in regulating cancer pathogenesis. Long non-coding RNAs (lncRNAs) are key regulators of gene expression and are involved in cancer progression and metastasis. However, the role of long non-coding RNAs (lncRNAs) in high-grade serous ovarian cancer (HGSC) is not well understood. We used the NCode™ non-coding RNA array to screen downregulated lncRNAs in HGSCs. After analyzing the array data of lncRNAs in HGSCs (n=29) and normal ovarian (n=11) samples, the probes mapping to the top 25 most down-regulated non-coding RNAs were analyzed. Two lncRNAs (ADAMTS9-AS1 and ADAMTS9-AS2) were identified as the antisense of gene ADAMTS9, and we validate by in vitro translation assay, q-RT-PCR, in-situ hybridization and the biological functions of ADAMTS9-AS2 in ovarian cancer cells. Moreover, using A2780-CP20 orthotopic mouse models of ovarian cancer, we further demonstrated restoring ADAMTS9-AS2 resulted in profound reduction of tumor growth and metastasis. Here, we demonstrate that ADAMTS9-AS2 is highly down-regulated (5.01x10 -13 and 1.6x10 -19 ) in ovarian cancers. Overexpression of ADAMTS9-AS2 leads to significantly increased apoptosis (7.5% control and 19.5% AS2OE) and decreased proliferation (49.5% control and 37.0% AS2OE) compared with controls. Consistently, increased expression of ADAMTS9-AS2 led to significantly reduced tumor burden in A2780-CP20 orthotopic ovarian cancer mouse models. We identified the promoter region of Annexin A1 as the major target of ADAMTS9-AS2. The binding of lncRNA ADAMTS9-AS2 to the promoter region can facilitate the expression of tumor suppressor Annexin A1 thereby decrease the proliferation and increase apoptosis of cancer cells. Collectively, our data point to an important role for ADAMTS9-AS2 as a tumor suppressor in ovarian cancer. Note: This abstract was not presented at the meeting. Citation Format: Cristian Rodriguez-Aguayo, Emine Bayraktar, Lingegowda S. Mangala, Cristina Ivan, Gabriel Lopez-Berestein, Anil K. Sood. Long non-coding RNA ADAMTS9-AS2 inhibits ovarian tumor growth via Annexin A1 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3579.