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LncRNA PVT1 regulates triple-negative breast cancer through KLF5/beta-catenin signaling

Oncogene volume 37, pages 4723–4734 (2018)Cite this article

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Recent molecularly targeted approach gains advance in breast cancer treatment. However, the estimated 5-year survival rate has not met the desired expectation for improvement, especially for patients with triple-negative breast cancer (TNBC). Here we report that the lncRNA PVT1 promotes KLF5/beta-catenin signaling to drive TNBC tumorigenesis. PVT1 is upregulated in clinical TNBC tumors. Using genetic approaches targeting PVT1 in TNBC cells, we found that PVT1 depletion inhibited cell proliferation, colony formation, and orthotopic xenograft tumor growth. Mechanistically, PVT1 binds with KLF5 and increases its stability via BAP1, which upregulates beta-catenin signaling, resulting in enhanced TNBC tumorigenesis. PVT1, KLF5, and beta-catenin were also revealed to be co-expressed in clinical TNBC samples. Our findings uncover a new singaling pathway to mediate TNBC, and provide PVT1 as a new target for improving treatment of TNBC.

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Acknowledgements

This work was supported in part by the National Natural Science Foundation of China (No. 81372704, 81572467 to H.F.; No.81470315, 81772663 to Y.L.); the Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning (No. 2014024), Shanghai Municipal Education Commission—Gaofeng Clinical Medicine Grant Support (No. 20161310), New Hundred Talent Program (Outstanding Academic Leader) at Shanghai Municipal Health Bureau (2017BR021), the State Key Laboratory of Oncogenes and Related Genes in China (No. 91-17-25), and Technology Transfer Project of Science and Technology Department at Shanghai Jiao Tong University School of Medicine (ZT201701) to H.F.; and Shanghai Jiao Tong University School of Medicine Hospital Fund (No. 14XJ10069) to Y.L.

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  1. State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China

    Jianming Tang, Youzhou Sang, Bo Yu, Deguan Lv, Weiwei Zhang & Haizhong Feng

  2. Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Pediatric Translational Medicine Institute, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China

    Yanxin Li

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  1. Jianming Tang
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Correspondence to Yanxin Li or Haizhong Feng.

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Tang, J., Li, Y., Sang, Y. et al. LncRNA PVT1 regulates triple-negative breast cancer through KLF5/beta-catenin signaling. Oncogene 37, 4723–4734 (2018). https://doi.org/10.1038/s41388-018-0310-4

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