MiR-5189-3p Suppresses Cell Proliferation, Invasion and Migration Through Targeting EIF5A2 in Laryngeal Squamous Cell Carcinoma

Overview

Journal Biochem Genet

Specialty Molecular Biology

Date 2023 Sep 1

PMID 37656330

Authors

Dan Lou

Qiaojing Jia

Haizhong Zhang

Jingmiao Wang

Lisha Liu

Zhichang Liu

XiaoFang Jia

Jianxing Wang

Chunguang Shan

Affiliations

Soon will be listed here.

Abstract

A growing body of evidence suggests that miR-5189-3p plays a critical role in multiple diseases. This study aimed to investigate the function of miR-5189-3p in laryngeal squamous cell carcinoma (LSCC) and explore its underlying mechanisms. qRT-PCR was designed to determine the expression levels of miR-5189-3p and eukaryotic translation initiation factor 5A2 (EIF5A2), while CCK-8 assay was performed to measure the effects of miR-5189-3p on cell proliferation. Transwell assay was performed to evaluate cell invasion as well as migration, and wound healing assay was applied to demonstrate cell migratory ability. Target gene prediction and luciferase reporter assay were developed to screen the possible target gene of miR-5189-3p, and Western blot was designed to measure EIF5A2 protein expression. MiR-5189-3p was down-regulated in LSCC tissues and cell lines. Up-regulation of miR-5189-3p notably inhibited cell proliferation, invasion, and migration in HEP2 and FADU cells. EIF5A2 was the potential downstream gene of miR-5189-3p, and overexpression of miR-5189-3p apparently reduced EIF5A2 expression. Moreover, reintroduction of EIF5A2 rescued the tumor suppressive effects of miR-5189-3p. MiR-5189-3p functions as a tumor inhibitor in LSCC progression via directly regulating EIF5A2 and may be a potential therapeutic target for LSCC.

References

Bao Y, Zhang Y, Lu Y, Guo H, Dong Z, Chen Q . Overexpression of microRNA-9 enhances cisplatin sensitivity in hepatocellular carcinoma by regulating EIF5A2-mediated epithelial-mesenchymal transition. Int J Biol Sci. 2020; 16(5):827-837. PMC: 7019138. DOI: 10.7150/ijbs.32460. View

Janiszewska J, Szaumkessel M, Szyfter K . microRNAs are important players in head and neck carcinoma: a review. Crit Rev Oncol Hematol. 2013; 88(3):716-28. DOI: 10.1016/j.critrevonc.2013.07.012. View

Johnson D, Burtness B, Leemans C, Lui V, Bauman J, Grandis J . Head and neck squamous cell carcinoma. Nat Rev Dis Primers. 2020; 6(1):92. PMC: 7944998. DOI: 10.1038/s41572-020-00224-3. View

Jung K, Narwal M, Min S, Keam B, Kang H . Squamous cell carcinoma of head and neck: what internists should know. Korean J Intern Med. 2020; 35(5):1031-1044. PMC: 7487309. DOI: 10.3904/kjim.2020.078. View

Koshizuka K, Hanazawa T, Arai T, Okato A, Kikkawa N, Seki N . Involvement of aberrantly expressed microRNAs in the pathogenesis of head and neck squamous cell carcinoma. Cancer Metastasis Rev. 2017; 36(3):525-545. DOI: 10.1007/s10555-017-9692-y. View

Lin S, Gregory R . MicroRNA biogenesis pathways in cancer. Nat Rev Cancer. 2015; 15(6):321-33. PMC: 4859809. DOI: 10.1038/nrc3932. View

Lu J, Fang Q, Ge X . Role and Mechanism of mir-5189-3p in Deep Vein Thrombosis of Lower Extremities. Ann Vasc Surg. 2021; 77:288-295. DOI: 10.1016/j.avsg.2021.07.004. View

Mathews M, Hershey J . The translation factor eIF5A and human cancer. Biochim Biophys Acta. 2015; 1849(7):836-44. PMC: 4732523. DOI: 10.1016/j.bbagrm.2015.05.002. View

Ning L, Wang L, Zhang H, Jiao X, Chen D . Eukaryotic translation initiation factor 5A in the pathogenesis of cancers. Oncol Lett. 2020; 20(4):81. PMC: 7436936. DOI: 10.3892/ol.2020.11942. View

10.

Pan Q, Zhao J, Li M, Liu X, Xu Y, Li W . Exosomal miRNAs are potential diagnostic biomarkers between malignant and benign thyroid nodules based on next-generation sequencing. Carcinogenesis. 2019; 41(1):18-24. DOI: 10.1093/carcin/bgz160. View

11.

Tian S, Yu J, Liu Y, Kang W, Ma Z, Ye X . MiR-30b suppresses tumor migration and invasion by targeting EIF5A2 in gastric cancer. World J Gastroenterol. 2015; 21(31):9337-47. PMC: 4541385. DOI: 10.3748/wjg.v21.i31.9337. View

12.

Wang F, Guan X, Xie D . Roles of eukaryotic initiation factor 5A2 in human cancer. Int J Biol Sci. 2013; 9(10):1013-20. PMC: 3831114. DOI: 10.7150/ijbs.7191. View

13.

Wu X, Cui C, Chen W, Fu Z, Cui X, Gong X . miR-144 suppresses the growth and metastasis of laryngeal squamous cell carcinoma by targeting IRS1. Am J Transl Res. 2016; 8(1):1-11. PMC: 4759411. View

14.

Wu G, Xu Y, Lau A . Recent insights into eukaryotic translation initiation factors 5A1 and 5A2 and their roles in human health and disease. Cancer Cell Int. 2020; 20:142. PMC: 7191727. DOI: 10.1186/s12935-020-01226-7. View

15.

Xu L, Chen Z, Xue F, Chen W, Ma R, Cheng S . MicroRNA-24 inhibits growth, induces apoptosis, and reverses radioresistance in laryngeal squamous cell carcinoma by targeting X-linked inhibitor of apoptosis protein. Cancer Cell Int. 2015; 15:61. PMC: 4477309. DOI: 10.1186/s12935-015-0217-x. View

16.

Yang Y, Cui H, Wang X . Downregulation of EIF5A2 by miR-221-3p inhibits cell proliferation, promotes cell cycle arrest and apoptosis in medulloblastoma cells. Biosci Biotechnol Biochem. 2018; 83(3):400-408. DOI: 10.1080/09168451.2018.1553604. View

17.

Yu X, Li Z . The role of microRNAs expression in laryngeal cancer. Oncotarget. 2015; 6(27):23297-305. PMC: 4695119. DOI: 10.18632/oncotarget.4195. View

18.

Zhang Y, Tu B, Sha Q, Qian J . Bone marrow mesenchymal stem cells-derived exosomes suppress miRNA-5189-3p to increase fibroblast-like synoviocyte apoptosis via the BATF2/JAK2/STAT3 signaling pathway. Bioengineered. 2022; 13(3):6767-6780. PMC: 8973596. DOI: 10.1080/21655979.2022.2045844. View