Long non-coding RNA NEAT1 transported by extracellular vesicles contributes to breast cancer development by sponging microRNA-141-3p and regulating KLF12

• Published in: Cell & bioscience Vol. 11; no. 1; p. 68
• Main Authors: Zhou, DaoPing, Gu, Juan, Wang, YuePing, Wu, HuaiGuo, Cheng, Wei, Wang, QingPing, Zheng, GuoPei, Wang, XueDong
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 05-04-2021; BioMed Central; BMC
• Subjects: 5-Fluorouracil; Age; Analysis; Breast cancer; Cancer; Cancer therapies; Cell cycle; Cell growth; Cell migration; Cell proliferation; Chemoresistance; Chemotherapy; Cisplatin; Drug resistance; Estrogen; Estrogen receptors; Extracellular vesicles; Gene expression; Health aspects; Invasion; Kruppel‐like factor 12; Lymph nodes; MDR1 protein; Membranes; Metastases; Metastasis; MicroRNA; microRNA-141-3p; MicroRNAs; miRNA; Non-coding RNA; Nuclear paraspeckle assembly transcript 1; P-Glycoprotein; Paclitaxel; Patients; Progesterone; Proteins; Public health; Canada; China; Beijing China; United States > US; Japan; Kruppel‐like factor 12; Chemotherapy resistance; microRNA-141-3p; Nuclear paraspeckle assembly transcript 1; Extracellular vesicles; Breast cancer; Metastasis; Invasion
• ISSN: 2045-3701; 2045-3701
• DOI: 10.1186/s13578-021-00556-x

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.
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.
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.
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.