A Micropeptide XBP1SBM Encoded by LncRNA Promotes Angiogenesis and Metastasis of TNBC Via XBP1s Pathway

Overview

Journal Oncogene

Specialties Molecular Biology
Oncology

Date 2022 Feb 24

PMID 35197570

Authors

Siqi Wu

Binbin Guo

Liyuan Zhang

Xun Zhu

Peipei Zhao

Jieqiong Deng

Jian Zheng

Fang Li

Yirong Wang

Shenghua Zhang

Zheng Zhang

Jiachun Lu

Yifeng Zhou

Affiliations

Soon will be listed here.

Abstract

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer (BC) with a poor prognosis. To date, the mechanism of TNBC's aggressive phenotype is still unclear. Based on metabolome analysis, we found that glutamine (Gln) metabolism plays a key role in the difference between TNBC and non-TNBC. We identified a 21-amino-acid survival-associated micropeptide XBP1SBM, encoded by the lncRNA MLLT4-AS1, which was upregulated in TNBC tissues and Gln-deprived TNBC cell lines. We showed that XBP1SBM expression was upregulated by Gln-deprivation-induced XBP1s transcriptional promotion, and in turn retained XBP1s in the nuclear to enhance the expression of VEGF. Using human endothelial cells, mouse xenograft models and mouse spontaneous BC models, we found that XBP1SBM improved Gln levels and promoted angiogenesis and metastasis in TNBC. Our study showed that a TNBC-specific nutrient deficiency adaption results in aggressive TNBC, and this mechanism provides a novel potential prognostic biomarker and therapeutic target in TNBC.

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