lncRNA UCA1 Contributes to 5-Fluorouracil Resistance of Colorectal Cancer Cells Through miR-23b-3p/ZNF281 Axis
Authors Xian Z, Hu B, Wang T, Zeng J, Cai J, Zou Q, Zhu P
Received 17 April 2020
Accepted for publication 22 June 2020
Published 31 July 2020 Volume 2020:13 Pages 7571—7583
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Dr Sanjay Singh
Zhenyu Xian,1,* Bang Hu,2,* Ting Wang,1 Junyi Zeng,1 Jinlin Cai,1 Qi Zou,2 Peixuan Zhu3
1Graceland Medical Center, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 2Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University (Gastrointestinal and Anal Hospital), Guangzhou, Guangdong, People’s Republic of China; 3International Medical Center, Guangzhou General Hospital of Foresea Life Insurance, Guangzhou, Guangdong, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Peixuan Zhu
International Medical Center, Guangzhou General Hospital of Foresea Life Insurance, 703 Xinchengdadao, Zengcheng District, Guangzhou 511300, Guangdong, People’s Republic of China
Tel +86 13682275819
Purpose: The chemoresistance of 5-fluorouracil (5-FU) limited the application of chemotherapy in colorectal cancer (CRC) treatment. Herein, we aimed to uncover the potential mechanism behind the 5-FU resistance of CRC cells.
Methods: The abundance of long noncoding RNA urothelial carcinoma associated 1 (lncRNA UCA1), microRNA-23b-3p (miR-23b-3p) and zinc finger protein 281 (ZNF281) was measured by quantitative real-time polymerase chain reaction (qRT-PCR) in CRC tissues and cells. Western blot was conducted to examine autophagy-related proteins, apoptosis-associated proteins and ZNF281 in CRC tissues and cells. Cell counting kit-8 (CCK8) assay was performed to detect the viability and inhibitory concentration 50% (IC50) value of 5-FU of CRC cells. The apoptosis of CRC cells was measured by flow cytometry. The binding sites between miR-23b-3p and UCA1 or ZNF281 were predicted by miRcode and Starbase software, respectively, and the combination was confirmed by dual-luciferase reporter assay and RIP assay. Murine xenograft model was established to verify the role of UCA1 on the 5-FU resistance of CRC in vivo.
Results: The 5-FU resistance of CRC was positively related to the level of UCA1 and autophagy. UCA1 accelerated the 5-FU resistance of CRC cells through facilitating autophagy and suppressing apoptosis. MiR-23b-3p was a target of UCA1 in 293T and CRC cells. The knockdown of miR-23b-3p reversed the inhibitory effects of UCA1 interference on the 5-FU resistance and autophagy and the promoting impact on the apoptosis of CRC cells. ZNF281 could bind to miR-23b-3p in 293T cells. MiR-23b-3p elevated the 5-FU sensitivity through down-regulating ZNF281 in CRC cells. UCA1 interference enhanced the 5-FU sensitivity of CRC through miR-23b-3p/ZNF281 axis in vivo.
Conclusion: UCA1 mediated 5-FU resistance of CRC cells through facilitating autophagy and inhibiting apoptosis via miR-23b-3p/ZNF281 axis in vivo and in vitro.
Keywords: colorectal cancer, 5-FU, UCA1, miR-23b-3p, ZNF281, autophagy, apoptosis
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