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PIWIL1 interacting RNA piR-017061 inhibits pancreatic cancer growth via regulating EFNA5

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Abstract

PIWI (P element induced wimpy testis) integrating RNAs (piRNAs) are small non-coding RNAs with the length of approximately 30 nucleotides that plays crucial roles in germ cells and adult stem cells. Recently, accumulating data have shown that piRNA and PIWI proteins are involved in tumorigenesis. However, the roles of PIWI proteins and piRNAs in pancreatic cancer are still elusive. Here, we showed that piR-017061 is significantly downregulated in pancreatic cancer patients’ samples and pancreatic cancer cell lines. Furthermore, we studied the function of piR-017061 in pancreatic cancer and our data revealed that piR-017061 inhibits pancreatic cancer cell growth in vitro and in vivo. Moreover, we analyzed the genomic loci around piR-017061 and identified EFNA5 as a novel target of piR-017061. Importantly, our data further revealed a direct binding between piR-017061 and EFNA5 mRNA mediated by PIWIL1. Mechanically, piR-017061 cooperates with PIWIL1 to facilitate EFNA5 mRNA degradation and loss of piR-017061 results in accumulation of EFNA5 which facilitates pancreatic cancer development. Hence, our data provided novel insights into PIWI/piRNA-mediated gene regulation and their function in pancreatic cancer. Since PIWI proteins and piRNA predominately express in germline and cancer cells, our study provided novel therapeutic strategy for pancreatic cancer treatment.

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Author notes

  1. Jing Xie and Shen Xing contributed equally to this work.

Authors and Affiliations

  1. Department of Pathology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China

    Jing Xie

  2. Ruijing Hospital Proton Therapy Center, Shanghai Jiaotong University School of Medicine, 868 Shuangding Road, Shanghai, 201800, China

    Shen Xing, Hai-Tao Chen & Bin Sun

  3. Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 868 Shuangding Road Shanghai, Shanghai, 201800, China

    Shen Xing, Bo-Yong Shen & Xiong-Xiong Lu

  4. Research Institute of Pancreatic Disease, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China

    Bo-Yong Shen & Xiong-Xiong Lu

  5. Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China

    Bo-Yong Shen & Xiong-Xiong Lu

  6. Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China

    Zheng-Ting Wang

  7. Suzhou Zhongjian AI Tech, 1888 Pangjing Road Suzhou, Suzhou, 215000, China

    Jing-Wang Wang

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  1. Jing Xie
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Correspondence to Jing-Wang Wang or Xiong-Xiong Lu.

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Involved patients were informed and all procedure related to patient samples and animals were approved by the Ethics Committee of Ruijin Hospital, Shanghai Jiaotong University School of Medicine and followed the Declaration of Helsinki. The approval number issued by the Ethics Committee of Ruijin Hospital is A-2019-016.

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Xie, J., Xing, S., Shen, BY. et al. PIWIL1 interacting RNA piR-017061 inhibits pancreatic cancer growth via regulating EFNA5. Human Cell 34, 550–563 (2021). https://doi.org/10.1007/s13577-020-00463-2

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