Long Non-coding RNA NEAT1 Transported by Extracellular Vesicles Contributes to Breast Cancer Development by Sponging MicroRNA-141-3p and Regulating KLF12

Overview

Journal Cell Biosci

Publisher Biomed Central

Specialty Biology

Date 2021 Apr 6

PMID 33820555

Citations 21

Authors

Daoping Zhou

Juan Gu

Yueping Wang

Huaiguo Wu

Wei Cheng

Qingping Wang

Guopei Zheng

Xuedong Wang

Affiliations

Soon will be listed here.

Abstract

Objective: Breast cancer (BC) remains a public-health issue on a global scale. Long non-coding RNAs (lncRNAs) play functional roles in BC. This study focuses on effects of NEAT1 on BC cell invasion, migration and chemotherapy resistance via microRNA (miR)-141-3p and KLF12.

Methods: After extraction and identification of serum extracellular vesicles (EVs), NEAT1 expression in EVs was detected and its association with clinical characteristics of BC patients was analyzed. Besides, the gain-of function was performed to investigate the roles of NEAT1 and miR-141-3p in BC, and levels of NEAT1, miR-141-3p, KLF12 and MDR1 after EV treatment were detected by RT-qPCR and Western blot analysis. Furthermore, the in vitro findings were confirmed via lung metastases in nude mice.

Results: NEAT1 expression in serum EVs was high and related to lymph node metastasis, progesterone receptor, estrogen receptor and Ki-67 in BC patients. After EV treatment, NEAT1 and KLF12 levels were increased, miR-141-3p expression was decreased, the abilities of proliferation, invasion, migration and in vivo metastasis were enhanced, and the sensitivity of cells to cisplatin, paclitaxel and 5-fluorouracil was decreased. After NEAT1 interference, NEAT1 and KLF12 levels in BC cells treated with EVs were decreased, miR-141-3p expression was increased, cell proliferation, invasion, migration and in vivo metastasis were decreased, and drug resistance sensitivity was increased. NEAT1 can bind to miR-141-3p and upregulates KLF12 expression.

Conclusions: EVs inhibit the regulation of KLF12 by miR-141-3p by transporting NEAT1 to BC cells, thus promoting BC cell invasion, migration, and chemotherapy resistance.

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