A Brain-enriched LncRNA Shields Cancer Cells from Immune-mediated Killing for Metastatic Colonization in the Brain

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2022 May 26

PMID 35617432

Authors

Weiguang Liu

Peng Sun

Lingling Xia

Xilin He

Zhengmiao Xia

Yehong Huang

Wenzhuo Liu

Lulu Li

Liming Chen

Affiliations

Soon will be listed here.

Abstract

Brain metastases, including prevalent breast-to-brain metastasis (B2BM), represent an urgent unmet medical need in the care of cancer due to a lack of effective therapies. Immune evasion is essential for cancer cells to metastasize to the brain tissue for brain metastasis. However, the intrinsic genetic circuits that enable cancer cells to avoid immune-mediated killing in the brain microenvironment remain poorly understood. Here, we report that a brain-enriched long noncoding RNA (BMOR) expressed in B2BM cells is required for brain metastasis development and is both necessary and sufficient to drive cancer cells to colonize the brain tissue. Mechanistically, BMOR enables cancer cells to evade immune-mediated killing in the brain microenvironment for the development of brain metastasis by binding and inactivating IRF3. In preclinical brain metastasis murine models, locked nucleic acid-BMOR, a designed silencer targeting BMOR, is effective in suppressing the metastatic colonization of cancer cells in the brain for brain metastasis. Taken together, our study reveals a mechanism underlying B2BM immune evasion during cancer cell metastatic colonization of brain tissue for brain metastasis, where B2BM cells evade immune-mediated killing in the brain microenvironment by acquiring a brain-enriched long noncoding RNA genetic feature.

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