Exosome-mediated transfer of lncRNA‑SNHG14 promotes trastuzumab chemoresistance in breast cancer
Authors: Ru Chen
Jing Han
Wei Wang
Kejian Zou
Huaying Dong
Xionghui He
Mulin Ye
Yu Zhang
Fan Zhang
Journal: International Journal of Oncology (2018)
Discipline: CLINICAL MEDICINE
Keywords: trastuzumab resistance; lncRNA; exosomes; breast cancer; SNHG14
Affiliations: Department of General Surgery, Hainan General Hospital, Haikou, Hainan 570311, P.R. China.

Abstract:  Currently, resistance to trastuzumab, a human epidermal growth factor receptor 2 (HER2) inhibitor, has become an important obstacle to improving the clinical outcome of patients with advanced HER2+ breast cancer. While cell behavior may be modulated by long non‑coding RNAs (lncRNAs), the contributions of lncRNAs within extracellular vesicles (exosomes) are largely unknown. To this end, the involvement and regulatory functions of potential lncRNAs contained within exosomes during the formation of chemoresistance in human breast cancer were investigated. Trastuzumab-resistant cell lines were established by continuously grafting HER2+ SKBR-3 and BT474 cells into trastuzumab-containing culture medium. An lncRNA microarray assay followed by reverse transcription‑quantitative polymerase chain reaction analysis identified that lncRNA-small nucleolar RNA host gene 14 (SNHG14) was upregulated in trastuzumab-resistant cells when compared with parental breast cancer cells. Functional experimentation demonstrated that knockdown of lncRNA‑SNHG14 potently promoted trastuzumab-induced cytotoxicity. Furthermore, extracellular lncRNA‑SNHG14 was able to be incorporated into exosomes and transmitted to sensitive cells, thus disseminating trastuzumab resistance. Treatment of sensitive cells with exosomes highly expressing lncRNA‑SNHG14 induced trastuzumab resistance, while knockdown of lncRNA‑SNHG14 abrogated this effect. The Signal Transduction Reporter Array indicated that lncRNA‑SNHG14 may promote the effect of trastuzumab by targeting the apoptosis regulator Bcl‑2 (Bcl‑2)/apoptosis regulator BAX (Bax) signaling pathway. Furthermore, the expression level of serum exosomal lncRNA‑SNHG14 was upregulated in patients who exhibited resistance to trastuzumab, compared with patients exhibiting a response. Therefore, lncRNA‑SNHG14 may be a promising therapeutic target for patients with HER2+ breast cancer. 

Retracted: Yes

PubPeer comments:
 The three sets of images in Figure 6C seem to have been published previously in Figure 2C of Oncotarget (2017), doi: 10.18632 oncotarget.15199. This paper was submitted about 1 month after the Oncotarget paper was published. I note that the authors appear to be physicians at a general hospital which would not be expected to have the facilities necessary to conduct the experiments of concern. Could the authors please comment? *** ![file] , 
 Retracted [9 June 2022] ).  Following the publication of this paper, it was drawn to the Editor s attention by a concerned reader that the TUNEL assay data shown in Fig. 6C were strikingly similar to images that had already appeared in Fig. 8B in another article that appeared in the journal *Oncotarget* [Chen W, Xu X-K, Li J-L, Kong K-K, Li H, Chen C, He J, Wang F, Li P, Ge X-S and Li F-C: MALAT1 is a prognostic factor in glioblastoma multiforme and induces chemoresistance to temozolomide through suppressing miR-203 and promoting thymidylate synthase expression. Oncotarget 8: 22783-22799, 2017]. Owing to the fact that the contentious data in the above article had already been published elsewhere prior to its submission to *International Journal of Oncology*, the Editor has decided that this paper should be retracted from the Journal on account of a lack of confidence in the presented data. The authors did provide an explanation to account for the duplication of the data, although this was not accepted by the Editorial Board. The Editor apologizes to the readership for any inconvenience caused. , 
 - *[left]* Fig 2A. - *[right]* Fig 4b 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 6b 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] ). - *[right]* **Fig 6B**. ![file] ,