<p>Lidocaine Suppresses Cell Proliferation and Aerobic Glycolysis by Regulating circHOMER1/miR-138-5p/HEY1 Axis in Colorectal Cancer</p>
Authors: Juan Du
Yang Wang
Hongzhong Ma
Pengpeng Wang
Liying Zhang
Journal: Cancer Management and Research (2020)
Discipline: CLINICAL MEDICINE
Keywords: CRC; HEY1; aerobic glycolysis; circHOMER1; lidocaine
Affiliations: Department of Anesthesiology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai 264000, Shandong, People's Republic of China.

Abstract:  Background: Increasing evidence has uncovered the anticancer activity of lidocaine in many cancers. However, the role and the underlying molecular mechanism of lidocaine in colorectal cancer (CRC) remain poorly understood. Materials and methods: Cell viability and apoptosis were measured by cell counting kit-8 assay and flow cytometry. Western blot was used to detect the protein of p53, CyclinD1, Pro-caspase-3, Cleaved-caspase-3, Pro-caspase-9, Cleaved-caspase-9, and hes-related family bHLH transcription factor with YRPW motif 1 (HEY1). Glycolytic metabolism was calculated by measuring the glucose consumption, lactate production and adenosine triphosphate (ATP) contents. The expression of circRNA homer scaffold protein 1 (circHOMER1), microRNA (miR)-138-5p and HEY1 mRNA was detected by quantitative real-time polymerase chain reaction. The interaction between miR-138-5p and circHOMER1 or HEY1 was analyzed using the dual-luciferase reporter assay. In vivo experiments were performed using the murine xenograft model. Results: Lidocaine suppressed CRC cell viability and aerobic glycolysis but promoted cell apoptosis in vitro as well as hindered tumor growth in vivo. CircHOMER1 was elevated in CRC tissues and cells, while lidocaine decreased circHOMER1 expression in CRC cells. Additionally, circHOMER1 overexpression reversed the anti-tumor activity of lidocaine in CRC cells. miR-138-5p was confirmed to interact with circHOMER1 and HEY1 in CRC cells directly, and circHOMER1 regulated HEY1 expression through repressing miR-138-5p expression. Besides, rescue assay indicated the anti-tumor activity mediated by lidocaine could be regulated by circHOMER1/miR-138-5p/HEY1 axis. Conclusion: Lidocaine mediated CRC cell viability loss, apoptosis induction and aerobic glycolysis inhibition by regulating circHOMER1/miR-138-5p/HEY1 axis, providing a novel treatment option for lidocaine to prevent the progression of CRC. 

Retracted: Yes

PubPeer comments:
 The Western blots in this paper have an atypical look, with pitch black smears and a mottled background. These atypical types of blots remind me of the patterns discussed in this post: https: scienceintegritydigest.com 2020 02 21 the-tadpole-paper-mill There is also one Figure (7F) with what appears to be a repeated band, although cropped differently. Would the authors please post an uncropped original scan of the gels illustrated in 7F? Also of note: the email address used by the corresponding author bears little resemblance to their name; another feature of some paper mill publishers. *** ![file] , 
 Thanks for your kind suggestion and comments. Due to the negligence of our work, the Western blots were pasted repeatedly when we made changes to figure7F. We have carefully revised the Western blots following the suggestion and provide the full uncropped and unedited versions of the Western blots. Look forward to hearing from you, sincerely. ![file] ![file] ![file] ![file] ![file] ![file] ![file] ![file] ![file] ![file] ![file] ![file] ![file] ![file] ![file] ![file] ![file] , 
 Thank you. I suggest you contact the journal. , 
 After speaking with other readers on social media, we are curious as to why your original *uncropped* images are cut out; see below for more typical originals. Could you describe the imaging process in more detail? *** ![file] , 
 #3 Thank you. I have contacted the journal. , 
 Sorry, comment left in wrong thread. , 
 #4 The raw uncropped WB blots showing the molecular markers have been provided to the magazine editor , 
 #7 Thank you for the update. Could you also supply those images here? , 
 2020 retraction. https: www.dovepress.com retraction-lidocaine-suppresses-cell-proliferation-and-aerobic-glycoly-peer-reviewed-article-CMAR Du J, Zhang L, Ma H, Wang Y, Wang P. Cancer Manag Res. 2020;12:5009u20135022. The Editor-in-Chief and Publisher of Cancer Management and Research wish to retract the published article. We were notified of the potential duplication of bands in the western blots shown for Figure 7F Pro-caspase-9 and GAPDH. The authors were unable to provide an adequate explanation and could not provide the satisfactory raw data. The editor had concerns regarding the overall integrity of the western blots and determined the findings of the study were no longer valid and requested for the article to be retracted. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as u201cRetractedu201d. ,