Long non-coding RNA NONHSAT101069 promotes epirubicin resistance, migration, and invasion of breast cancer cells through NONHSAT101069/miR-129-5p/Twist1 axis
Authors: Jing He
Zhao Liu
Lie Chen
Na Yao
Shui Wang
Yichao Zhu
Yue Fu
Tiansong Xia
Journal: Oncogene (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Drug resistance; epirubicin; breast cancer; epithelial-mesenchymal transition (EMT); long non-coding RNAs (lncRNAs)
Affiliations: Breast Disease Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu Province, P. R. China., Department of Thyroid & Breast Surgery, The Affiliated Hospital of Nanjing University of TCM, Wuxi City Hospital of TCM, Wuxi, 214000, Jiangsu Province, P. R. China., Department of General Surgery, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou, 213000, Jiangsu Province, P. R. China., Department of Thyroid & Breast Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 222100, Jiangsu Province, P. R. China., Department of Surgical Oncology, The Affiliated Hospital of Jiangnan University, Wuxi, 214000, Jiangsu Province, P. R. China., Department of Physiology, Nanjing Medical University, Nanjing, 211166, Jiangsu Province, P. R. China. ., State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, 211166, Jiangsu Province, P. R. China. ., Breast Disease Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu Province, P. R. China. .

Abstract:  Drug resistance, including epirubicin-based therapeutic resistance, is one of the major reasons responsible for the unfavorable prognosis of patients diagnosed with breast cancer (BC). Acquired chemoresistance and metastatic properties have been identified to be closely associated with the process of epithelial-mesenchymal transition (EMT). Recently, dysregulation of long non-coding RNAs (lncRNAs) have been increasingly reported to perform promotive or suppressive functions in chemoresistance and EMT process in multiple cancers. However, relevant novel lncRNA participating in epirubicin resistance and EMT and its underlying molecular mechanisms remain unknown in BC. Herein, we established the epirubicin-resistant breast cancer cell subline (MCF-7/ADR), which presented mesenchymal phenotype and increased metastatic potential. A panel of differentially expressed lncRNAs, including 268 upregulated and 49 downregulated lncRNAs, were identified by high-flux microarray investigation in MCF-7 and MCF-7/ADR cells. The novel lncRNA NONHSAT101069 was significantly overexpressed in BC specimens, BC cell lines, and epirubicin-resistant cell sublines. The knockdown of NONHSAT101069 significantly repressed, whereas overexpression of NONHSAT101069 promoted the epirubicin resistance, migration, invasion and EMT process of BC cells both in vitro and in vivo. Further mechanism-related researches uncovered that NONHSAT101069 functioned as a ceRNA (competing endogenous RNA) via sponging miR-129-5p. Twist1 was a direct downstream protein of NONHSAT101069/miR-129-5p axis in BC cells. To conclude, NONHSAT101069 was upregulated in BC tissues and promoted epirubicin resistance, migration and invasion of BC cells via regulation of NONHSAT101069/miR-129-5p/Twist1 axis, highlighting its potential as an oncogene and a therapeutic biomarker for BC. 

Retracted: No

PubPeer comments:
 A micrograph has been duplicated and presented as something else (Figure 3c vs Figure 6d). ![file] , 
 Thanks for your comments on the images of Boyden chamber assays. We have checked the original data of Boyden chamber assays immediately and make sure that this is not a subjective forgery. This error had been made when we were compiling the picture of Fig. 3c (invasion of MCF-7 control group). We apologize for our mistake. We are in the process of formally correcting this mistake. ,