长链非编码 RNA PVT1 通过 KLF5/β-连环蛋白信号通路调控三阴性乳腺癌。
LncRNA PVT1 regulates triple-negative breast cancer through KLF5/beta-catenin signaling.
机构信息
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.
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.
出版信息
Oncogene. 2018 Aug;37(34):4723-4734. doi: 10.1038/s41388-018-0310-4. Epub 2018 May 15.
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.
最近的分子靶向方法在乳腺癌治疗方面取得了进展。然而，估计的 5 年生存率并没有达到预期的改善水平，特别是对于三阴性乳腺癌（TNBC）患者。在这里，我们报告长链非编码 RNA PVT1 促进 KLF5/β-连环蛋白信号转导以驱动 TNBC 肿瘤发生。PVT1 在临床 TNBC 肿瘤中上调。通过针对 TNBC 细胞中的 PVT1 采用遗传方法，我们发现 PVT1 耗竭抑制细胞增殖、集落形成和原位异种移植肿瘤生长。在机制上，PVT1 通过 BAP1 与 KLF5 结合并增加其稳定性，从而上调 β-连环蛋白信号转导，导致增强的 TNBC 肿瘤发生。在临床 TNBC 样本中还揭示了 PVT1、KLF5 和 β-连环蛋白的共表达。我们的研究结果揭示了一种新的信号通路来介导 TNBC，并为改善 TNBC 的治疗提供了新的靶点。
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