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

Cell & Bioscience

HuaiGuo Wu¹  Wei Cheng¹  DaoPing Zhou¹  QingPing Wang¹  GuoPei Zheng¹  YuePing Wang²  XueDong Wang³  Juan Gu⁴ 

[1] Center for Precision Medicine, Anhui No.2 Provincial People’s Hospital, 230041, Hefei, Anhui, China;Center for Precision Medicine, Anhui No.2 Provincial People’s Hospital, 230041, Hefei, Anhui, China;Department of Biology, College of Arts & Science, Massachusetts University, 02125, Boston, MA, USA;Center for Precision Medicine, Anhui No.2 Provincial People’s Hospital, 230041, Hefei, Anhui, China;Department of Medical Laboratory Science, The Fifth People’s Hospital of Wuxi, Nanjing Medical University, 1215 Guangrui Road, 214000, Wuxi, Jiangsu, China;Department of Medical Laboratory Science, The Fifth People’s Hospital of Wuxi, Nanjing Medical University, 1215 Guangrui Road, 214000, Wuxi, Jiangsu, China;Department of Pathology, The Fifth People’s Hospital of Wuxi, The Medical School of Jiangnan University, 214000, Wuxi, Jiangsu, China;

关键词: Breast cancer;    Extracellular vesicles;    Nuclear paraspeckle assembly transcript 1;    microRNA-141-3p;    Kruppel‐like factor 12;    Invasion;    Metastasis;    Chemotherapy resistance;   

DOI  :  10.1186/s13578-021-00556-x

来源: Springer

【 摘 要 】

ObjectiveBreast 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.MethodsAfter 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.ResultsNEAT1 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.ConclusionsEVs inhibit the regulation of KLF12 by miR-141-3p by transporting NEAT1 to BC cells, thus promoting BC cell invasion, migration, and chemotherapy resistance.

【 授权许可】

CC BY