MicroRNA‑544 inhibits esophageal squamous cell carcinoma cell proliferation and enhances sensitivity to cisplatin by repressing E2F transcription factor 5

Sun,Fengrong; Zhang,Cuiping; Ma,Deliang; Wang,Kai

doi:10.3892/ol.2019.10749

MicroRNA‑544 inhibits esophageal squamous cell carcinoma cell proliferation and enhances sensitivity to cisplatin by repressing E2F transcription factor 5

Authors:
- Fengrong Sun
- Cuiping Zhang
- Deliang Ma
- Kai Wang
View Affiliations

Affiliations: Department of Oncology, Linyi Central Hospital, Linyi, Shandong 276400, P.R. China, Department of Breast Surgery, Weifang People's Hospital, Weifang, Shandong 261041, P.R. China
Published online on: August 16, 2019 https://doi.org/10.3892/ol.2019.10749
Pages: 4203-4209
Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies worldwide. MicroRNA (miRNA)‑544 is an important cancer‑associated RNA that is downregulated in multiple types of cancer. However, the role of miR‑544 in ESCC progression remains unknown. In the present study, miR‑544 expression level was determined via RT‑qPCR in 30 pairs of ESCC and adjacent normal tissues and in a panel of ESCC cell lines. Cell proliferation and cell apoptosis were assessed by MTT and flow cytometry assays. Luciferase reporter assay and western blot analysis were conducted to verify E2F transcription factor 5 (E2F5), an oncogene in ESCC, as a novel target gene of miR‑544. The results illustrated that miR‑544 is frequently downregulated in ESCC tissues and cell lines. Overexpression of miR‑544 in ESCC cells resulted in decreased cell proliferation and increased cell apoptosis. Thus, E2F5 was identified as a target of miR‑544, and its expression was negatively correlated with miR‑544 expression in clinical ESCC tissues. More importantly, overexpression of miR‑544 led to increased sensitivity of ESCC cells to cisplatin, an anticancer drug. Overall, these findings indicate that miR‑544 serves as a tumor suppressor by targeting E2F5; thus, miR‑544 may be a therapeutic target for the treatment of ESCC.

View Figures

View References

1	Siegel RL, Miller KD and Jemal A: Cancer Statistics, 2017. CA Cancer J Clin. 67:7–30. 2017. View Article : Google Scholar : PubMed/NCBI
2	Enzinger PC and Mayer RJ: Esophageal cancer. N Engl J Med. 349:2241–2252. 2003. View Article : Google Scholar : PubMed/NCBI
3	Abnet CC, Arnold M and Wei WQ: Epidemiology of esophageal squamous cell carcinoma. Gastroenterology. 154:360–373. 2018. View Article : Google Scholar : PubMed/NCBI
4	Baba Y, Saeki H, Nakashima Y, Oki E, Shigaki H, Yoshida N, Watanabe M, Maehara Y and Baba H: Review of chemotherapeutic approaches for operable and inoperable esophageal squamous cell carcinoma. Dis Esophagus. 30:1–7. 2017.
5	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
6	Mei LL, Qiu YT, Zhang B and Shi ZZ: MicroRNAs in esophageal squamous cell carcinoma: Potential biomarkers and therapeutic targets. Cancer Biomark. 19:1–9. 2017. View Article : Google Scholar : PubMed/NCBI
7	Harada K, Baba Y, Ishimoto T, Shigaki H, Kosumi K, Yoshida N, Watanabe M and Baba H: The role of microRNA in esophageal squamous cell carcinoma. J Gastroenterol. 51:520–530. 2016. View Article : Google Scholar : PubMed/NCBI
8	Chen M, Liu YY, Zheng MQ, Wang XL, Gao XH, Chen L and Zhang GM: microRNA-544 promoted human osteosarcoma cell proliferation by downregulating AXIN2 expression. Oncol Lett. 15:7076–7082. 2018.PubMed/NCBI
9	Pan C, Xiang L, Pan Z, Wang X, Li J, Zhuge L, Fang P, Xie Q and Hu X: MiR-544 promotes immune escape through downregulation of NCR1/NKp46 via targeting RUNX3 in liver cancer. Cancer Cell Int. 18:522018. View Article : Google Scholar : PubMed/NCBI
10	Yao GD, Zhang YF, Chen P and Ren XB: MicroRNA-544 promotes colorectal cancer progression by targeting forkhead box O1. Oncol Lett. 15:991–997. 2018.PubMed/NCBI
11	Zhi Q, Guo X, Guo L, Zhang R, Jiang J, Ji J, Zhang J, Zhang J, Chen X, Cai Q, et al: Oncogenic miR-544 is an important molecular target in gastric cancer. Anticancer Agents Med Chem. 13:270–275. 2013. View Article : Google Scholar : PubMed/NCBI
12	Zhu Z, Wang S, Zhu J, Yang Q, Dong H and Huang J: MicroRNA-544 down-regulates both Bcl6 and Stat3 to inhibit tumor growth of human triple negative breast cancer. Biol Chem. 397:1087–1095. 2016. View Article : Google Scholar : PubMed/NCBI
13	Jin S, Dai Y, Li C, Fang X, Han H and Wang D: MicroRNA-544 inhibits glioma proliferation, invasion and migration but induces cell apoptosis by targeting PARK7. Am J Transl Res. 8:1826–1837. 2016.PubMed/NCBI
14	Sobin LH, Gospodarowicz MK and Wittekind C: International union against cancer (UICC) TNM classification of malignant tumoursWiley-Liss; New York: pp. 73–76. 2010
15	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
16	Fang R, Zhao NN, Zeng KX, Wen Q, Xiao P, Luo X, Liu XW and Wang YL: MicroRNA-544 inhibits inflammatory response and cell apoptosis after cerebral ischemia reperfusion by targeting IRAK4. Eur Rev Med Pharmacol Sci. 22:5605–5613. 2018.PubMed/NCBI
17	Ren B, Cam H, Takahashi Y, Volkert T, Terragni J, Young RA and Dynlacht BD: E2F integrates cell cycle progression with DNA repair, replication and G(2)/M checkpoints. Genes Dev. 16:245–256. 2002. View Article : Google Scholar : PubMed/NCBI
18	Kothandaraman N, Bajic VB, Brendan PN, Huak CY, Keow PB, Razvi K, Salto-Tellez M and Choolani M: E2F5 status significantly improves malignancy diagnosis of epithelial ovarian cancer. BMC Cancer. 10:642010. View Article : Google Scholar : PubMed/NCBI
19	Ishimoto T, Shiozaki A, Ichikawa D, Fujiwara H, Konishi H, Komatsu S, Kubota T, Okamoto K, Nakashima S, Shimizu H, et al: E2F5 as an independent prognostic factor in esophageal squamous cell carcinoma. Anticancer Res. 33:5415–5420. 2013.PubMed/NCBI
20	Zhao J, Wu XY, Ling XH, Lin ZY, Fu X, Deng YH, He HC and Zhong W: Analysis of genetic aberrations on chromosomal region 8q21-24 identifies E2F5 as an oncogene with copy number gain in prostate cancer. Med Oncol. 30:4652013. View Article : Google Scholar : PubMed/NCBI
21	Jiang Y, Yim SH, Xu HD, Jung SH, Yang SY, Hu HJ, Jung CK and Chung YJ: A potential oncogenic role of the commonly observed E2F5 overexpression in hepatocellular carcinoma. World J Gastroenterol. 17:470–477. 2011. View Article : Google Scholar : PubMed/NCBI
22	Lin C, Hu Z, Yuan G, Su H, Zeng Y, Guo Z, Zhong F, Jiang K and He S: MicroRNA-1179 inhibits the proliferation, migration and invasion of human pancreatic cancer cells by targeting E2F5. Chem Biol Interact. 291:65–71. 2018. View Article : Google Scholar : PubMed/NCBI
23	Li L, Wu C and Zhao Y: miRNA-34a enhances the sensitivity of gastric cancer cells to treatment with paclitaxel by targeting E2F5. Oncol Lett. 13:4837–4842. 2017. View Article : Google Scholar : PubMed/NCBI