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Upregulation of miR-494 Inhibits Cell Growth and Invasion and Induces Cell Apoptosis by Targeting Cleft Lip and Palate Transmembrane 1-Like in Esophageal Squamous Cell Carcinoma

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Abstract

Background

Potential target genes of microRNA (miR)-494 have been reported in many types of cancers. However, the role of miR-494 in esophageal squamous cell carcinoma (ESCC) remains unknown.

Aim

This study focused on the expression and biological function of miR-494 in ESCC.

Methods

Using bioinformatics analyses, we found that cleft lip and palate transmembrane 1-like (CLPTM1L) was a potential target of miR-494. We performed quantitative real-time (qRT) PCR assays in 37 ESCC tumor tissues to determine the expression of miR-494 and CLPTM1L mRNA, and we analyzed the correlation between both of these factors and clinical characteristics. The cell counting kit-8 and colony formation assays were used to evaluate the effects of miR-494 expression on the proliferation of ESCC cells. The transwell migration assay and flow cytometric apoptosis assay were performed to study the influence of miR-494 on the invasion and apoptosis of ESCC cells. Western blotting, luciferase assays, and CLPTM1L knockdown experiments were used to determine whether CLPTM1L was a target of miR-494.

Results

The qRT-PCR assays showed significant downregulation of miR-494 (P < 0.05) and upregulation of CLPTM1L mRNA (P < 0.05), both of which were significantly associated with lymph node metastases (P < 0.05). High expression of miR-494 inhibited cell proliferation and invasion and promoted cell apoptosis (P < 0.05). The results also showed that CLPTM1L was a target of miR-494.

Conclusion

These results show that the expression of miR-494, which can regulate cell growth, invasion and apoptosis of ESCC cells by targeting CLPTM1L, is downregulated in ESCC tumor tissues. The miR-494–CLPTM1L pathway could be further exploited to develop a new approach to treat ESCC.

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References

  1. Coleman HG, Bhat S, Murray LJ, et al. Increasing incidence of Barrett’s oesophagus: a population-based study. Eur J Epidemiol. 2011;26:739–745.

    Article  PubMed  Google Scholar 

  2. Umar SB, Fleischer DE. Esophageal cancer: epidemiology, pathogenesis and prevention. Nat Clin Pract Gastroenterol Hepatol. 2008;5:517–526.

    Article  Google Scholar 

  3. Zhang Y. Epidemiology of esophageal cancer. World J Gastroenterol. 2013;14:5598–5606.

    Article  Google Scholar 

  4. Ward MH, Cross AJ, Abnet CC, et al. Heme iron from meat and risk of adenocarcinoma of the esophagus and stomach. Eur J Cancer Prev. 2012;21:134–138.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Cross AJ, Freedman ND, Ren J, et al. Meat consumption and risk of esophageal and gastric cancer in a large prospective study. Am J Gastroenterol. 2011;106:432–442.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Zhu X, Ding M, Yu ML, et al. Identification of galectin-7 as a potential biomarker for esophageal squamous cell carcinoma by proteomic analysis. BMC Cancer. 2010;10:290.

    Article  PubMed Central  PubMed  Google Scholar 

  7. Zhou ZQ, Cao WH, Xie JJ, et al. Expression and prognostic significance of THBS1, Cyr61 and CTGF in esophageal squamous cell carcinoma. BMC Cancer. 2009;9:291.

    Article  PubMed Central  PubMed  Google Scholar 

  8. Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993;75:843–854.

    Article  CAS  PubMed  Google Scholar 

  9. Ambros V. The functions of animal microRNAs. Nature. 2004;431:350–355.

    Article  CAS  PubMed  Google Scholar 

  10. Hobert O. Gene regulation by transcription factors and microRNAs. Science. 2008;319:1785–1786.

    Article  CAS  PubMed  Google Scholar 

  11. Meister G. miRNAs get an early start on translational silencing. Cell. 2007;131:25–28.

    Article  CAS  PubMed  Google Scholar 

  12. Farazi TA, Spitzer JI, Morozov P, et al. miRNAs in human cancer. J Pathol. 2011;223:102–115.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Zhang Q, Sun H, Jiang Y, et al. MicroRNA-181a suppresses mouse granulosa cell proliferation by targeting activin receptor IIA. PLoS One. 2013;8:e59667.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Huang Y, Zou Q, Song H, et al. A study of miRNAs targets prediction and experimental validation. Protein Cell. 2010;1:979–986.

    Article  CAS  PubMed  Google Scholar 

  15. Wang C, Lu S, Jiang J, et al. Hsa-microRNA-101 suppresses migration and invasion by targeting Rac1 in thyroid cancer cells. Oncol Lett. 2014;8:1815–1821.

    PubMed Central  CAS  PubMed  Google Scholar 

  16. Lei SL, Zhao H, Yao HL, et al. Regulatory roles of microRNA-708 and microRNA-31 in proliferation, apoptosis and invasion of colorectal cancer cells. Oncol Lett. 2014;8:1768–1774.

    PubMed Central  CAS  PubMed  Google Scholar 

  17. Takamizawa J, Konishi H, Yanagisawa K, et al. Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res. 2004;64:3753–3756.

    Article  CAS  PubMed  Google Scholar 

  18. Shen PF, Chen XQ, Liao YC, et al. MicroRNA-494-3p targets CXCR4 to suppress the proliferation, invasion, and migration of prostate cancer. Prostate. 2014;74:756–767.

    Article  CAS  PubMed  Google Scholar 

  19. He W, Li Y, Chen X, et al. miR-494 acts as an anti-oncogene in gastric carcinoma by targeting c-myc. J Gastroenterol Hepatol. 2014;29:1427–1434.

    Article  CAS  PubMed  Google Scholar 

  20. Romano G, Acunzo M, Garofalo M, et al. miR-494 is regulated by ERK1/2 and modulates TRAIL-induced apoptosis in non-small-cell lung cancer through BIM down-regulation. Proc Natl Acad Sci USA. 2012;109:16570–16575.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Guo Y, Chen Z, Zhang L, et al. Distinctive microRNA profiles relating to patient survival in esophageal squamous cell carcinoma. Cancer Res. 2008;68:26–33.

    Article  CAS  PubMed  Google Scholar 

  22. Wang Z, Qiao Q, Chen M, et al. miR-625 down-regulation promotes proliferation and invasion in esophageal cancer by targeting Sox2. FEBS Lett. 2014;588:915–921.

    Article  CAS  PubMed  Google Scholar 

  23. Ogawa R, Ishiguro H, Kuwabara Y, et al. Expression profiling of micro-RNAs in human esophageal squamous cell carcinoma using RT-PCR. Med Mol Morphol. 2009;42:102–109.

    Article  CAS  PubMed  Google Scholar 

  24. Akagi I, Miyashita M, Ishibashi O, et al. Relationship between altered expression levels of MIR21, MIR143, MIR145, and MIR205 and clinicopathologic features of esophageal squamous cell carcinoma. Dis Esophagus. 2011;24:523–530.

    Article  CAS  PubMed  Google Scholar 

  25. Hummel R, Hussey DJ, Michael MZ, et al. miRNAs and their association with locoregional staging and survival following surgery for esophageal carcinoma. Ann Surg Oncol. 2011;18:253–260.

    Article  PubMed  Google Scholar 

  26. Prescott J, Wentzensen IM, Savage SA, et al. Epidemiologic evidence for a role of telomere dysfunction in cancer etiology. Mutat Res. 2012;730:75–84.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Rafnar T, Sulem P, Stacey SN, et al. Sequence variants at the TERT-CLPTM1L locus associate with many cancer types. Nat Genet. 2009;41:221–227.

    Article  CAS  PubMed  Google Scholar 

  28. Yamamoto K, Okamoto A, Isonishi S, et al. A novel gene, CRR9, which was up-regulated in CDDP-resistant ovarian tumor cell line, was associated with apoptosis. Biochem Biophys Res Commun. 2001;280:1148–1154.

    Article  CAS  PubMed  Google Scholar 

  29. Lu X, Ke J, Luo X, et al. The SNP rs402710 in 5p15.33 is associated with lung cancer risk: a replication study in Chinese population and a meta-analysis. PLoS One. 2013;8:e76252.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. James MA, Wen W, Wang Y, et al. Functional characterization of CLPTM1L as a lung cancer risk candidate gene in the 5p15.33 locus. PLoS One. 2012;7:e36116.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Petersen Gloria M, Amundadottir Laufey, Fuchs Charles S, et al. A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33. Nat Genet. 2010;42:224–228.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by the National Natural Science Foundation of China (No. 81272188 and No. 81301726).

Conflict of interest

None.

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Authors and Affiliations

  1. College of Basic Medical Sciences, Zhengzhou University, No. 100 Kexue Road, Zhengzhou, 450001, Henan, China

    Ren Zhang, Xiaonan Chen, Shengjie Zhang, Xueyan Zhang, Tong Li, Wenqiao Zang, Yuanyuan Wang, Yuwen Du & Guoqiang Zhao

  2. Oncology Department, The Tumor Hospital of Linzhou City, Linzhou, 456500, Henan, China

    Zhicai Liu & Jinwu Wang

Authors
  1. Ren Zhang
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  2. Xiaonan Chen
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  3. Shengjie Zhang
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  4. Xueyan Zhang
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  5. Tong Li
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  6. Zhicai Liu
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  7. Jinwu Wang
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  9. Yuanyuan Wang
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  11. Guoqiang Zhao
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Correspondence to Guoqiang Zhao.

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Zhang, R., Chen, X., Zhang, S. et al. Upregulation of miR-494 Inhibits Cell Growth and Invasion and Induces Cell Apoptosis by Targeting Cleft Lip and Palate Transmembrane 1-Like in Esophageal Squamous Cell Carcinoma. Dig Dis Sci 60, 1247–1255 (2015). https://doi.org/10.1007/s10620-014-3433-7

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  • DOI: https://doi.org/10.1007/s10620-014-3433-7

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