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GALNT5 uaRNA promotes gastric cancer progression through its interaction with HSP90

Oncogene volume 37, pages 4505–4517 (2018)Cite this article

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Abstract

Recently, long noncoding RNAs (lncRNAs) have been reported to play a pivotal role in the occurrence and progression of cancer because of their unique characteristics and have therefore become an active area of cancer research. The object of this study was to screen lncRNAs that are dysregulated in gastric cancer and to investigate their potential functions. Global expression of lncRNAs in gastric cancer and adjacent normal tissues of patients was profiled using a microarray assay. We identified an lncRNA (GALNT5 uaRNA, UTR-associated RNA) that is derived from the 3′-UTR of GALNT5. This lncRNA was transcribed independently of the coding region of GALNT5 and was determined to be markedly upregulated in human gastric carcinoma relative to their corresponding normal gastric tissues by quantitative RT-PCR (qRT-PCR) analysis of tissues from 122 gastric carcinoma patients. The expression of GALNT5 uaRNA was significantly correlated with the TNM stage and with lymph node metastasis. Further results demonstrated that GALNT5 uaRNA facilitated the proliferation and migration of gastric cancer cells in vitro and promoted tumor growth in a mouse model of human gastric cancer. Our results also indicated that GALNT5 uaRNA might function in gastric cancer by binding with HSP90. Further studies indicated that the 5′-end stem-loop motifs of GALNT5 uaRNA promoted the binding of HSP90 and its client proteins, and thus inhibited ubiquitination of the clients. These results expanded our understanding of GALNT5 uaRNA as a new avenue for therapeutic intervention against gastric cancer progression.

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Funding

This work was partially supported by the Natural Science Foundation of China (Grant No. 81572755, 81372200 to J. Shi), CAMS Initiative for Innovative Medicine (CAMS-I2M Grant No. 2016-I2M-1-001to J. Shi).

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Author notes

  1. These authors contributed equally: Hui Guo, Lianmei Zhao, Bianhua Shi.

Authors and Affiliations

  1. National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100005, China

    Hui Guo, Lianmei Zhao, Bianhua Shi, Jiayu Bao, Dexian Zheng & Juan Shi

  2. Research Center, the Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, China

    Lianmei Zhao

  3. Department of General Surgery, the First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, China

    Baoguo Zhou

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  1. Hui Guo
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Correspondence to Baoguo Zhou or Juan Shi.

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Guo, H., Zhao, L., Shi, B. et al. GALNT5 uaRNA promotes gastric cancer progression through its interaction with HSP90. Oncogene 37, 4505–4517 (2018). https://doi.org/10.1038/s41388-018-0266-4

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