Expression of Concern Issued: Exosome-Mediated Transfer of Long Noncoding RNA HOTAIR Regulates Temozolomide Resistance by miR-519a-3p/RRM1 Axis in Glioblastoma

Cancer Biotherapy and Radiopharmaceuticals (CBR) issues a formal Expression of Concern pertaining to a published article (online ahead of print) entitled, “Exosome-Mediated Transfer of Long Noncoding RNA HOTAIR Regulates Temozolomide Resistance by miR-519a-3p/RRM1 Axis in Glioblastoma” by Zhihai Yuan, Zhen Yang, Weiqin Li, Aimei Wu, Zhixiang Su, and Bin Jiang (epub 24 Jul 2020; doi: 10.1089/cbr.2019.3499). Readers are advised that the CBR editorial office received conflicting requests via email from the corresponding author, Dr. Bin Jiang, to “withdraw” the paper. One email indicated that, “due to our negligence, we have a series of conflicts of interest in this article, [sic]” while another email reads, “my team need to explore more on the given aspect of manuscript, [sic]” but did not provide explanations or details. Several attempts were made by the editorial office and the publisher to contact the individual coauthors listed on the paper, utilizing the email addresses on file from the time of submission, asking each author for their respective agreements to Dr. Jiang's request to “withdraw” the paper. Three of the authors listed on the paper responded to the publisher's inquiry agreeing to the withdrawal, however, they were not from the email addresses on file with the journal so they could not be verified. The publisher also asked Dr. Jiang for the name(s) and contact information of the department Chair(s) and/or Dean(s) of the authors institutions, including his own, but no response to that particular inquiry was received except for Dr. Jiang's continued emails requesting the withdrawal of the article. Independent analyses were also run on the images appearing in the paper which found that there are duplicated western blots between Figures 1 and 2. Since the request to “withdraw” the paper was from the corresponding author and because there has been difficulty securing all coauthors agreements to do so, in addition to the inconsistent messaging from Dr. Jiang, the Editor of CBR has determined that an Expression of Concern is warranted at this time instead of an official retraction or withdrawal. If clearer details emerge, or if all authors agree to a retraction, one will be issued accordingly. The authors were notified that this Expression of Concern was to be issued, but no acknowledgment was received. Background: Chemoresistance obstructs the treatment of glioblastoma (GB). Exosome-mediated transfer of long noncoding RNAs (lncRNAs) was reported to regulate chemoresistance in diverse cancers. The authors aimed to investigate the underlying mechanism of lncRNA HOX transcript antisense intergenic RNA (HOTAIR) in regulating temozolomide (TMZ) resistance in GB. Materials and Methods: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was utilized to check TMZ resistance and cell proliferation. The abilities of cell migration and invasion were evaluated by transwell assay. The protein levels of E-cadherin, N-cadherin, Vimentin, CD63, CD81, and ribonucleoside-diphosphate reductase subunit M1 (RRM1) were measured by Western blot. Quantitative real-time polymerase chain reaction was conducted to detect the levels of HOTAIR, microRNA (miR)-519a-3p, and RRM1. The starBase was hired to predict the target sites between miR-519a-3p and HOTAIR or RRM1 and the dual-luciferase reporter assay was performed to verify the interaction. Xenograft tumor model was established to investigate the biological role of HOTAIR in vivo. Results: The high abilities of cell viability and metastasis were observed in TMZ-resistant GB cells. LncRNA HOTAIR was significantly upregulated in TMZ-resistant GB cells and its downregulation inhibited proliferation, migration, invasion, and epithelial/mesenchymal transition in TMZ-resistant GB cells. Further analysis indicated that exosomal lncRNA HOTAIR induced TMZ resistance and modulated TMZ resistance through miR-519a-3p/RRM1 axis. Besides, serum exosomal lncRNA HOTAIR was stable and had diagnostic value. Moreover, knockdown of lncRNA HOTAIR reduced TMZ resistance in vivo. Conclusions: Exosomal lncRNA HOTAIR mediated TMZ resistance through miR-519a-3p/RRM1 axis in GB.