LncRNA PVT1 Regulates Triple-negative Breast Cancer Through KLF5/beta-catenin Signaling

Overview

Journal Oncogene

Specialties Molecular Biology
Oncology

Date 2018 May 16

PMID 29760406

Citations 91

Authors

Jianming Tang

Yanxin Li

Youzhou Sang

Bo Yu

Deguan Lv

Weiwei Zhang

Haizhong Feng

Affiliations

Soon will be listed here.

Abstract

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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