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miRNA-181a-5p Enhances the Sensitivity of Cells to Cisplatin in Esophageal Adenocarcinoma by Targeting CBLB

Authors Yang S, Wang P, Wang S, Cong A, Zhang Q, Shen W, Li X, Zhang W, Han G

Received 25 February 2020

Accepted for publication 16 May 2020

Published 25 June 2020 Volume 2020:12 Pages 4981—4990

DOI https://doi.org/10.2147/CMAR.S251264

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Eileen O'Reilly


Song Yang,1,* Peng Wang,1,* Songhua Wang,1 Aihua Cong,1 Qi Zhang,1 Wenhao Shen,1 Xiangyi Li,2 Wei Zhang,3 Gaohua Han1

1Department of Oncology, Taizhou People’s Hospital, Taizhou, Jiangsu 225300, People’s Republic of China; 2Department of Endocrinology, Taizhou People’s Hospital, Taizhou, Jiangsu 225300, People’s Republic of China; 3Department of Infectious Diseases, Taizhou People’s Hospital, Taizhou 225300, Jiangsu, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Wei Zhang; Gaohua Han Email tgc6nl@163.com; y0ztiin@163.com

Background: Cisplatin (CDDP) is extensively used for esophageal adenocarcinoma (EAC) chemotherapy, while cisplatin resistance is getting worse. microRNA-181a-5p (miR-181a-5p) has been reported to play an important role in various human cancers. However, the effect and underlying mechanism of miR-181a-5p in cisplatin resistance of EAC remain unclear.
Methods: Cisplatin-resistant EAC cells OE19/CDDP and parental sensitive OE19 cells were applied for experiments in vitro. The expressions of miR-181a-5p and CBLB were measured by quantitative real-time polymerase chain reaction (qRT-PCR) or Western blot. The cisplatin resistance of cells was expressed by cell viability, IC50 and apoptosis rate by using CCK-8 assay or flow cytometry. The interaction between miR-181a-5p and CBLB was evaluated by luciferase reporter assay and RIP assay. In vivo experiments were conducted via the murine xenograft model.
Results: miR-181a-5p was highly expressed while CBLB was lowly expressed in OE19 cell lines compared with OE19/CDDP cells. In cisplatin-resistant OE19/CDDP cells, miR-181a-5p up-regulation or CBLB knockdown inhibited cell viability and inducted apoptosis. In cisplatin-sensitive OE19 cells, miR-181a-5p inhibition or CBLB overexpression promoted cell viability and suppressed apoptosis. CBLB was confirmed to be a target of miR-181a-5p, and rescue assay showed CBLB overexpression reversed the suppression of OE19/CDDP cell viability induced by miR-181a-5p up-regulation, and its down-regulation attenuated miR-181a-5p-inhibition-mediated enhancement of OE19 cell viability. In addition, miR-181a-5p up-regulation enhanced the cytotoxicity of cisplatin in EAC in vivo.
Conclusion: miR-181a-5p enhanced the sensitivity of cells to cisplatin in EAC by targeting CBLB, indicating a promising sensitizer of cisplatin therapy in clinical esophageal cancer.

Keywords: EAC, cisplatin resistance, miR-181a-5p, CBLB


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