Long non‐coding RNA SNHG14 induces trastuzumab resistance of breast cancer via regulating PABPC1 expression through H3K27 acetylation
Authors: Shaowei Mo
Ru Chen
Qiang Liu
Xin Chen
Jing Han
Wei Wang
Kejian Zou
Huaying Dong
Xionghui He
Mulin Ye
Jianguo Hu
Yu Zhang
Fan Zhang
Journal: Journal of Cellular and Molecular Medicine (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: H3K27 acetylation; PABPC1; SNHG14; breast cancer; trastuzumab resistance.
Affiliations: Department of General Surgery, Hainan General Hospital, Jinan University, Haikou, China., Department of Science and Education, Hainan Maternal and Child Health Hospital, Haikou, China., Department of Pharmacy, Hainan Medical University, Haikou, China., Department of General Surgery, The Frist Affiliated Hospital, Chongqing Medical University, Chongqing, China., Department of Obstetrics and Gynecology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.

Abstract:  Currently, resistance to trastuzumab, a human epidermal growth factor receptor 2 (HER2) inhibitor, has become one major obstacle for improving the clinical outcome of patients with advanced HER2+ breast cancer. While cell behaviour can be modulated by long non-coding RNAs (lncRNAs), the contributions of lncRNAs in progression and trastuzumab resistance of breast cancer are largely unknown. To this end, the involvement and regulatory functions of lncRNA SNHG14 in human breast cancer were investigated. RT-qPCR assay showed that SNHG14 was up-regulated in breast cancer tissues and associated with trastuzumab response. Gain- and loss-of-function experiments revealed that overexpression of SNHG14 promotes cell proliferation, invasion and trastuzumab resistance, whereas knockdown of SNHG14 showed an opposite effect. PABPC1 gene was identified as a downstream target of SNHG14, and PABPC1 mediates the SNHG14-induced oncogenic effects. More importantly, ChIP assays demonstrated that lncRNA SNHG14 may induce PABPC1 expression through modulating H3K27 acetylation in the promoter of PABPC1 gene, thus resulting in the activation of Nrf2 signalling pathway. These data suggest that lncRNA SNHG14 promotes breast cancer tumorigenesis and trastuzumab resistance through regulating PABPC1 expression through H3K27 acetylation. Therefore, SNHG14 may serve as a novel diagnostic and therapeutic target for breast cancer patients. 

Retracted: No

PubPeer comments:
 There appears to be an unexpected duplication in Figures 2H and 4E. ![file] , 
 - *[left]* Fig 1B from  from  Long nonu2010coding RNA SNHG14 induces trastuzumab resistance of breast cancer via regulating PABPC1 expression through H3K27 acetylation ([Zhang et al 2018] . - *[right]* **Fig 3A**. ![file] , 
 - *[left]* Fig 3E. - *[right]* Fig 5E from  Discovery and validation of the tumor-suppressive function of long noncoding RNA PANDA in human diffuse large B-cell lymphoma through the inactivation of MAPK ERK signaling pathway ([Wang et al 2017] ). ![file] , 
 Clockwise from upper left: - Fig 2D. - Fig 5G from  Discovery and validation of the tumor-suppressive function of long noncoding RNA PANDA in human diffuse large B-cell lymphoma through the inactivation of MAPK ERK signaling pathway ([Wang et al 2017] ). - Fig 3F from  Identification and functional characterization of circRNA-0008717 as an oncogene in osteosarcoma through sponging miR-203 ([Zhou et al 2018] ). - Fig 3d from  Exosome-mediated transfer of lncRNA PART1 induces gefitinib resistance in esophageal squamous cell carcinoma via functioning as a competing endogenous RNA ([Kang et al 2018] ). ![file] , 
 - *[left]* **Fig 4C**. - *[right]* Fig 6E from  Identification and functional characterization of circRNA-0008717 as an oncogene in osteosarcoma through sponging miR-203 ([Zhou et al 2018] ). ![file] - *[upper left]* Fig 3C from  Exosome-mediated transfer of lncRNA RP11u2011838N2.4 promotes erlotinib resistance in non-small cell lung cancer ([Zhang et al 2018] ). - *[upper right]* Fig 7B from  MALAT1 is a prognostic factor in glioblastoma multiforme and induces chemoresistance to temozolomide through suppressing miR-203 and promoting thymidylate synthase expression ([Chen et al 2017] ). - *[below]* **Fig 4B**. ![file] - *[left]* Fig 3D from  SP1-induced lncRNA AGAP2-AS1 expression promotes chemoresistance of breast cancer by epigenetic regulation of MyD88 ([Dong et al 2018] ). - *[right]* Fig 7H from  Exosome-mediated transfer of lncRNA PART1 induces gefitinib resistance in esophageal squamous cell carcinoma via functioning as a competing endogenous RNA ([Kang et al 2018] ). ![file] , 
 #1 Figs 2H, 4E again: ![] Another version of a panel appears in Fig 2E of  Angelica Sinensis Polysaccharide Suppresses Epithelial-Mesenchymal Transition and Pulmonary Fibrosis via a DANCR AUF-1 FOXO3 Regulatory Axis ([Qian et al 2019] ). ![file] , 
 - *[left]* Fig 2G. - *[right]* Fig 1f from  Activation of LncRNA TINCR by H3K27 acetylation promotes Trastuzumab resistance and epithelial-mesenchymal transition by targeting MicroRNA-125b in breast Cancer ([Dong et al 2019] ) **[retracted]**. ![file] , 
 Fig 5F. ![file] Fig 2E from  lncRNA ZEB1-AS1 Mediates Oxidative Low-Density Lipoprotein-Mediated Endothelial Cells Injury by Post-transcriptional Stabilization of NOD2 ([Xu et al 2019] ). ![file] Left to right: - Fig 2f from  Exosome-mediated transfer of lncRNA PART1 induces gefitinib resistance in esophageal squamous cell carcinoma via functioning as a competing endogenous RNA ([Kang et al 2019] ). - Fig 2F from  Exosome-mediated transfer of lncRNA RP11-838N2.4 promotes erlotinib resistance in non-small cell lung cancer ([Zhang et al 2018] ). - Fig 4C from  SP1-induced lncRNA AGAP2-AS1 expression promotes chemoresistance of breast cancer by epigenetic regulation of MyD88 ([Dong et al 2018] ). ![file] , 
 - *[left]* Fig 7B. - *[right]* Fig 7h from  Exosome-mediated lncRNA AFAP1-AS1 promotes trastuzumab resistance through binding with AUF1 and activating ERBB2 translation ([Han et al 2020] ) **[retracted]**. ![file] , 
 - *[left]* Fig 4F from  lncRNA ZNF649-AS1 Induces Trastuzumab Resistance by Promoting ATG5 Expression and Autophagy ([Han et al 2020] ). - *[right]* **Fig 2E**. ![file] , 
 #5 #9 ![] Another sighting of the bands: Figs 1B, 4C from  Exosome-mediated transfer of lncRNAu2011SNHG14 promotes trastuzumab chemoresistance in breast cancer ([Dong et al 2018] ) **[retracted]**. ![file] ,