Genome-wide Target Interactome Profiling Reveals a Novel Epigenetic Pathway for Oncogenic LncRNA in Breast Cancer

Overview

Journal Am J Cancer Res

Specialty Oncology

Date 2019 May 21

PMID 31105998

Citations 26

Authors

Xueli Li

Naifei Chen

Lei Zhou

Cong Wang

Xue Wen

Lin Jia

Jiuwei Cui

Andrew R Hoffman

Ji-Fan Hu

Wei Li

Affiliations

Soon will be listed here.

Abstract

Breast cancer is the most common cancer in women worldwide, accounting for approximately 500,000 deaths each year. is a highly conserved long noncoding RNA (lncRNA), and its increased expression is associated with relapse and metastatic progression in breast cancer. We performed RNA reverse transcription-associated trap sequencing (RAT-seq) to characterize the genome-wide target interaction network for and showed that interacted with multiple pathway target genes that are closely related to tumor progression and metastasis. Notably, bound to the promoter regulatory element of the translation elongation factor 1-alpha 1 gene . Knockdown of by shRNA caused significant downregulation of in breast cancer MDA-MB231 and SKRB3 cells. Using a luciferase reporter assay, we showed that knockdown of reduced the promoter activity of in these two breast cancer cells. Chromatin immunoprecipitation (ChIP) assay indicated that regulated by altering the histone 3 lysine 4 (H3K4) epigenotype in the gene promoter. was overexpressed in breast cancer tissues and breast cancer cells. Knockdown of reduced cell proliferation and invasion by arresting cells at the G0/G1 phase. Ectopic overexpression of reversed the altered tumor phenotypes induced by shRNA treatment. These data suggest an epigenetic mechanism by which lncRNA facilitates a pro-metastatic phenotype in breast cancer by -regulating .

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