circ_0136666 Facilitates the Progression of Colorectal Cancer via miR-383/CREB1 Axis
Authors Li Y, Zang H, Zhang X, Huang G
Received 29 February 2020
Accepted for publication 9 July 2020
Published 4 August 2020 Volume 2020:12 Pages 6795—6806
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 4
Editor who approved publication: Dr Ahmet Emre Eskazan
Yuhui Li, Hongliang Zang, Xue Zhang, Guomin Huang
Department of General Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of China
Correspondence: Guomin Huang
Department of General Surgery, China-Japan Union Hospital of Jilin University, No. 829 Xinmin Avenue, Changchun, Jilin 130012, People’s Republic of China
Background: The changes in dietary patterns cause an increased incidence of colorectal cancer (CRC) globally. We aimed to explore the mechanism behind circular RNA circ_0136666 in the progression of CRC.
Materials and Methods: The expression of circ_0136666, miR-383 and cAMP response element binding protein 1 (CREB1) was detected by real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferation, apoptosis and glycolysis were measured by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry and glucose or lactate detection kit, respectively. The combination between miR-383 and circ_0136666 or CREB1 in 293T cells was predicted by Circular RNA Interactome or Starbase software and confirmed by dual-luciferase reporter assay. Western blot assay was performed to detect the abundance of CREB1, hexokinase 2 (HK2) and lactate dehydrogenase A (LDHA) in CRC cells. Murine xenograft model was established to verify the function of circ_0136666 in vivo.
Results: circ_0136666 was aberrantly up-regulated in CRC tissues and cells, and it promoted the proliferation and glycolysis and inhibited the apoptosis of CRC cells. circ_0136666 accelerated the progression of CRC through directly targeting and down-regulating miR-383. CREB1 could bind to miR-383 in 293T cells. The overexpression of CREB1 reversed the inhibitory effects of miR-383 accumulation on the proliferation and glycolysis and the promoting impact on the apoptosis of CRC cells. The enrichment of CREB1 was modulated by circ_0136666/miR-383 signaling in CRC cells. The glycolysis-related proteins (HK2 and LDHA) were modulated by circ_0136666/miR-383/CREB1 axis in CRC cells. circ_0136666 accelerated the growth of CRC tumors via circ_0136666/miR-383/CREB1 axis in vivo.
Conclusion: circ_0136666 deteriorated CRC through miR-383/CREB1 axis. circ_0136666/miR-383/CREB1 axis might be an underlying therapeutic target for CRC therapy.
Keywords: colorectal cancer, circ_0136666, miR-383, CREB1, proliferation, apoptosis, glycolysis
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.Download Article [PDF] View Full Text [HTML][Machine readable]