Lidocaine Suppresses Cell Proliferation and Aerobic Glycolysis by Regulating circHOMER1/miR-138-5p/HEY1 Axis in Colorectal Cancer
Authors Du J, Zhang L, Ma H, Wang Y, Wang P
Received 6 January 2020
Accepted for publication 28 May 2020
Published 25 June 2020 Volume 2020:12 Pages 5009—5022
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Eileen O'Reilly
This paper has been retracted.
Juan Du,* Liying Zhang,* Hongzhong Ma, Yang Wang, Pengpeng Wang
Department of Anesthesiology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai 264000, Shandong, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Hongzhong Ma Tel +86-535-6691999
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.
Keywords: circHOMER1, miR-138-5p, HEY1, CRC, lidocaine, aerobic glycolysis
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