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Mantang Qiu



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    Lunch & Poster Display session (ID 58)

    • Event: ELCC 2019
    • Type: Poster Display session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 4/11/2019, 12:30 - 13:00, Hall 1
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      5P - The circular RNA circXPO1 promotes tumor growth in lung adenocarcinoma (ID 293)

      12:30 - 13:00  |  Author(s): Mantang Qiu

      • Abstract
      • Slides

      Background

      Circular RNAs (circRNA), a subclass of noncoding RNA characterized by covalently closed continuous loops, play emerging roles in tumorigenesis and aggressiveness. Somatic copy number variations (CNV) may drive cancer progression through both coding and noncoding transcripts. In lung adenocarcinomas, tumor stage is positively correlated with the proportion of CNV. CNV-associated circRNAs in lung cancer have rarely been reported.

      a9ded1e5ce5d75814730bb4caaf49419 Methods

      To identify critical circRNAs that contribute to lung adenocarcinoma progression, ribosomal RNA-depleted RNA sequencing was performed in 5 paired lung adenocarcinoma tissues and adjacent non-tumor tissues. Maltose-binding protein (MBP)-affinity purification and RNA immunoprecipitation (RIP) were used to identify RNA-binding proteins (RBPs) that were associated with circXPO1. Patient-derived xenograft (PDX) models were performed to assess the clinical benefits of targeting circXPO1.

      20c51b5f4e9aeb5334c90ff072e6f928 Results

      By integrating bioinformatics analyses of alerted circRNAs and focal CNV in lung adenocarcinoma, we identify a proto-oncogenic circular RNA (circXPO1), produced from the XPO1 gene at 2p15 amplicon. CircXPO1 was overexpressed in lung adenocarcinoma tissues and promoted proliferation and tumorigenesis of lung adenocarcinoma. Our mechanistic studies indicated that circXPO1 functions, at least in part, through its interaction with IGF2BP1. CircXPO1 epigenetically upregulated β-Catenin expression in lung adenocarcinoma cancer cells by interacting with IGF2BP1 to promote the stabilization of β-Catenin. Intratumor injection of cholesterolconjugated siRNA specifically targeting circXPO1 inhibited tumor growth in a patient-derived lung adenocarcinoma xenograft model.

      fd69c5cf902969e6fb71d043085ddee6 Conclusions

      In summary, our study identified a CNV-associated circular RNA, circXPO1, which is overexpressed in lung adenocarcinoma tissues, due to the amplification of 2q15 locus, promotes proliferation and tumorigenesis of lung adenocarcinoma via interacting with IGF2BP1 and subsequently promote the stabilization of β-Catenin. Meanwhile, understanding the precise role of circXPO1 provides a novel therapeutic strategy for lung adenocarcinoma in the sight of circular RNAs.

      b651e8a99c4375feb982b7c2cad376e9 Legal entity responsible for the study

      Qi Huang, Mantang Qiu, Fan Yang, Jun Wang.

      213f68309caaa4ccc14d5f99789640ad Funding

      National Natural Science Foundation of China.

      682889d0a1d3b50267a69346a750433d Disclosure

      All authors have declared no conflicts of interest.

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