J Cancer 2020; 11(21):6337-6347. doi:10.7150/jca.50587

Research Paper

miR-424-5p regulates cell proliferation and migration of esophageal squamous cell carcinoma by targeting SIRT4

Ying Cui1,2*, Jiani Yang2,3*, Yibing Bai2,3*, Yanqiao Zhang2,3✉*, Yuanfei Yao2,3, Tongsen Zheng2,3, Chao Liu2,3, Feng Wu2,4

1. Department of Radiation Oncology, Harbin Medical University Cancer Hospital, Harbin, China.
2. Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, China.
3. Department of Gastrointestinal Medical oncology, Harbin Medical University Cancer Hospital, Harbin, China.
4. Department of Gastroenterology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
*These authors contributed equally to this study.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Cui Y, Yang J, Bai Y, Zhang Y, Yao Y, Zheng T, Liu C, Wu F. miR-424-5p regulates cell proliferation and migration of esophageal squamous cell carcinoma by targeting SIRT4. J Cancer 2020; 11(21):6337-6347. doi:10.7150/jca.50587. Available from http://www.jcancer.org/v11p6337.htm

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Objective: The present research is aimed to elucidate the expression patterns of miR-424-5p and its role in tumorigenesis and progression of esophageal squamous cell carcinoma (ESCC).

Methods: Both starBase and TCGA were utilized to assess miR-424-5p expression status in ESCC. The endogenous mRNA expression levels of miR-424-5p in ESCC and normal esophagus cell lines were detected by qRT-PCR. CCK8 and colony-forming assays were applied to determine the effects of miR-424-5p on ESCC proliferation. Transwell migration and wound healing assays were carried out to observe the changes of ESCC cell mobility after miR-424-5p mimic or inhibitor transfection. Impact of miR-424-5p on malignancy growth in vivo was further verified in a mouse xenograft model. The regulatory relationships between miR-424-5p and SIRT4 were validated by dual luciferase reporter assay, qRT-PCR and Western blot.

Results: miR-424-5p expression was found upregulated in ESCC. miR-424-5p overexpression dramatically facilitated ESCC cells proliferation and migration capacity in vitro, while downregulation of miR-424-5p displayed the opposite trend. Inhibition of xenograft tumor growth was further evidenced in vivo. Moreover, SIRT4 was confirmed to be a specific target gene of miR-424-5p in ESCC and negatively modulated by miR-424-5p. Finally, SIRT4 overexpression strongly rescued the promoting influence of miR-424-5p on the proliferative and migratory capacity of ESCC cells.

Conclusions: miR-424-5p had tumor promoting functions in proliferation and migration of ESCC by targeting SIRT4, suggesting that miR-424-5p may serve as a potential diagnostic biomarker and manipulation of miR-424-5p/SIRT4 axis could provide a novel therapeutic strategy for further ESCC treatment.

Keywords: esophageal squamous cell carcinoma, ESCC, miR-424-5p, SIRT4, in vivo