Tumor Biology

, Volume 37, Issue 12, pp 16135–16140 | Cite as

MicroRNA-153 inhibits tumor progression in esophageal squamous cell carcinoma by targeting SNAI1

  • Jing Zuo
  • Dahu Wang
  • Haitao Shen
  • Fengling Liu
  • Jing Han
  • Xianghong Zhang
Original Article


One of the important mediators of Epithelial to mesenchymal transition (EMT) is the Snail1 protein (encoded by SNAI1) which facilitates transition to mesenchymal state by transcriptionally repressing the epithelial cell marker E-cadherin. Given its central role in EMT and tumor metastasis, the cell has evolved multiple levels of regulatory mechanism at transcriptional, post-transcriptional, and post-translational level to regulate SNAI1 expression. Recently, miR-153 has been shown to regulate SNAI1 expression in hepatocellular carcinoma. The objective of the current study was to determine if SNAI1 expression in esophageal squamous cell carcinoma (ESCC) is regulated by miR-153. Metagenomic analysis of The Cancer Genome Atlas (TCGA) data identified an inverse correlation between miR-153 and SNAI1 expression in ESCC. Our study showed that the expression of miR-153 was noticeably downregulated in the ESCC cell line investigated and tissues, compared with normal esophageal epithelial cells and matched adjacent non-tumorous esophageal tissue. We demonstrated that miR-153 downregulated Snail expression by directly targeting the 3′-untranslated region (3′UTR) of SNAI1, which could be rescued by the use of miR-153 mimic and antagomir in ESCC cell line and normal esophageal epithelial cells, respectively. MiR-153 mimic inhibited the migration and invasion ability of ESCC cells whereas miR-153 antagomir promoted migration and invasion of normal esophageal epithelial cell line. Finally, overexpression of miR-153 in the ESCC cell line significantly attenuated experimental lung metastasis as assessed by tail vein injection in xenograft assay. Cumulatively, our data indicate that suppression of miR-153 dictates SNAI1 upregulation during EMT and metastatic progression of ESCC.




Compliance with ethical standards

Conflicts of interest



  1. 1.
    Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63:11–30.CrossRefPubMedGoogle Scholar
  2. 2.
    Chen Y, Zhu SM, XL X, Zhao AN, Hu JL. Expression levels of HER2 and MRP1 are not prognostic factors of long-term survival in 829 patients with esophageal squamous cell carcinoma. Oncol Lett. 2016;11:745–52.PubMedGoogle Scholar
  3. 3.
    Sawada G, Niida A, Uchi R, et al. Genomic landscape of esophageal squamous cell carcinoma in a japanese population. Gastroenterology. 2016;150(5):1171–82. doi: 10.1053/j.gastro.2016.01.035
  4. 4.
    Cunningham D, Allum WH, Stenning SP, et al. MAGIC trial participants: perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355:11–20.CrossRefPubMedGoogle Scholar
  5. 5.
    Omloo JM, Lagarde SM, Hulscher JB, et al. Extended transthoracic resection compared with limited transhiatal resection for adenocarcinoma of the mid/distal esophagus: five-year survival of a randomized clinical trial. Ann Surg. 2007;246:992–1001.CrossRefPubMedGoogle Scholar
  6. 6.
    Kuo KT, Chou TY, Hsu HS, Chen WL, Wang LS. Prognostic significance of NBS1 and snail expression in esophageal squamous cell carcinoma. Ann Surg Oncol. 2012;19(Suppl 3):S549–57.CrossRefPubMedGoogle Scholar
  7. 7.
    Natsugoe S, Uchikado Y, Okumura H, et al. Snail plays a key role in E-cadherin-preserved esophageal squamous cell carcinoma. Oncol Rep. 2007;17:517–23.PubMedGoogle Scholar
  8. 8.
    Zheng H, Kang Y. Multilayer control of the EMT master regulators. Oncogene. 2014;33:1755–63.CrossRefPubMedGoogle Scholar
  9. 9.
    Zheng H, Shen M, Zha YL, et al. PKD1 phosphorylation-dependent degradation of SNAIL by SCF-FBXO11 regulates epithelial-mesenchymal transition and metastasis. Cancer Cell. 2014;26:358–73.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Xia W, Ma X, Li X, et al. miR-153 inhibits epithelial-to-mesenchymal transition in hepatocellular carcinoma by targeting Snail. Oncol Rep. 2015;34:655–62.PubMedGoogle Scholar
  11. 11.
    Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009;136:215–33.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Esquela-Kerscher A, Slack FJ. Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer. 2006;6:259–69.CrossRefPubMedGoogle Scholar
  13. 13.
    Aleckovic M, Kang Y. Regulation of cancer metastasis by cell-free miRNAs. Biochim Biophys Acta. 2015;1855:24–42.PubMedGoogle Scholar
  14. 14.
    Gaur A, Jewell DA, Liang Y, et al. Characterization of microRNA expression levels and their biological correlates in human cancer cell lines. Cancer Res. 2007;67:2456–68.CrossRefPubMedGoogle Scholar
  15. 15.
    Kumar MS, Lu J, Mercer KL, Golub TR, Jacks T. Impaired microRNA processing enhances cellular transformation and tumorigenesis. Nat Genet. 2007;39:673–7.CrossRefPubMedGoogle Scholar
  16. 16.
    Lu J, Getz G, Miska EA, et al. MicroRNA expression profiles classify human cancers. Nature. 2005;435:834–8.CrossRefPubMedGoogle Scholar
  17. 17.
    Zhao JY, Wang F, Li Y, et al. Five miRNAs considered as molecular targets for predicting esophageal cancer. Med Sci Monit. 2015;21:3222–30.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Chen WJ, Zhang EN, Zhong ZK, et al. MicroRNA-153 expression and prognosis in non-small cell lung cancer. Int J Clin Exp Pathol. 2015;8:8671–5.PubMedPubMedCentralGoogle Scholar
  19. 19.
    Fkih M’hamed I, Privat M, Ponelle F, Penault-Llorca F, Kenani A, Bignon YJ. Identification of miR-10b, miR-26a, miR-146a and miR-153 as potential triple-negative breast cancer biomarkers. Cell Oncol (Dordr). 2015;38:433–42.CrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Jing Zuo
    • 1
  • Dahu Wang
    • 2
  • Haitao Shen
    • 3
  • Fengling Liu
    • 1
  • Jing Han
    • 1
  • Xianghong Zhang
    • 3
  1. 1.Department of OncologyThe Fourth Hospital of Hebei Medical UniversityShijiazhuangChina
  2. 2.Department of DermatologyThe Second Hospital of Hebei Medical UniversityShijiazhuangChina
  3. 3.Department of PathologyHebei Medical UniversityShijiazhuangChina

Personalised recommendations