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Aloperine Inhibits Proliferation and Promotes Apoptosis in Colorectal Cancer Cells by Regulating the circNSUN2/miR-296-5p/STAT3 Pathway

Authors Han W, Kong D, Lu Q, Zhang W, Fan Z

Received 12 November 2020

Accepted for publication 16 January 2021

Published 25 February 2021 Volume 2021:15 Pages 857—870

DOI https://doi.org/10.2147/DDDT.S288473

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Anastasios Lymperopoulos


Wei Han,1– 3,* Desong Kong,2,* Qin Lu,4 Wei Zhang,5 Zhimin Fan4

1Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 2Chinese Medicine Modernization and Big Data Research Center, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 3General Surgery Department, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 4Proctology Department, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 5Anesthesiology Department, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Zhimin Fan
Proctology Department, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, No. 157 Daming Avenue, Qinhuai District, Nanjing City, Jiangsu Province, 210012, People’s Republic of China
Tel +86-2552276501
Email [email protected]

Background: Aloperine can regulate miR-296-5p/Signal Transducer and Activator of Transcription 3 (STAT3) pathway to inhibit the malignant development of colorectal cancer (CRC), but the regulatory mechanism is unclear. This study explored the upstream mechanism of Aloperine in reducing CRC damage from the perspective of the circRNA-miRNA-mRNA regulatory network.
Methods: After treatment with gradient concentrations of Aloperine (0.1 mmol/L, 0.2 mmol/L, 0.4 mmol/L, 0.8 mmol/L and 1 mmol/L) for 24 hours, changes in CRC cell proliferation and apoptosis were detected by functional experiments. Data of the differential expression of miR-296-5p in CRC patients and healthy people were obtained from Starbase. The effects of Aloperine on 12 differentially expressed circRNAs were detected. The binding of miR-296-5p with NOP2/Sun RNA methyltransferase 2 (circNSUN2) and STAT3 was predicted by TargetScan and confirmed through dual-luciferase experiments. The expressions of circNSUN2, miR-296-5p and STAT3 as well as apoptosis-related genes in CRC cells were detected by qRT-PCR and Western blot as needed. Rescue experiments were conducted to test the regulatory effects of circNSUN2, miR-296-5p and STAT3 on CRC cells.
Results: Aloperine at a concentration gradient inhibited proliferation and promoted apoptosis in CRC cells. The abnormally low expression of miR-296-5p in CRC could be upregulated by Aloperine. Among the differentially expressed circRNAs in CRC, only circNSUN2 not only targets miR-296-5p, but also can be regulated by Aloperine. The up-regulation of circNSUN2 offset the inhibitory effect of Aloperine on cancer cells. The rescue experiments finally confirmed the regulation of circNSUN2/miR-296-5p/STAT3 axis in CRC cells.
Conclusion: By regulating the circNSUN2/miR-296-5p/STAT3 pathway, Aloperine prevents the malignant development of CRC cells.

Keywords: colorectal cancer, aloperine, NOP2/Sun RNA methyltransferase 2, miR-296-5p, signal transducer and activator of transcription 3

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