Skip to main content

Advertisement

SpringerLink
Log in

MicroRNA-145 and MicroRNA-133a Inhibited Proliferation, Migration, and Invasion, While Promoted Apoptosis in Hepatocellular Carcinoma Cells Via Targeting FSCN1

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Background

Deregulation of FSCN1 has been observed in human cancers. However, the regulatory mechanism of FSCN1 in hepatocellular carcinoma (HCC) remains largely unknown.

Aims

Our study aimed to reveal the roles of microRNA (miR)-133a, miR-145, and FSCN1 in HCC cells.

Methods

Real-time RT-PCR and western blot were performed to determine the expression of miR-133a, miR-145, and FSCN1. Luciferase reporter assay was used to determine whether FSCN1 was a target of miR-133a and miR-145. Effects of miR-133a, miR-145, and FSCN1 on HCC cell proliferation, apoptosis, migration, and invasion were then investigated.

Results

We showed that the expression of FSCN1 was increased in HCC tissues compared to the normal adjacent tissues. Moreover, upregulation of FSCN1 and downregulation of miR-145 and miR-133a co-existed in HCC. Functional studies revealed that miR-145 and miR-133a negatively regulated the expression of FSCN1 in HCC cells, via directly binding to the 3′-untranslational region of FSCN1 mRNA. Overexpression of miR-145 and miR-133a led to decreased FSCN1 expression, and downregulation of miR-145 and miR-133a resulted in increased FSCN1 expression in HCC cells. Furthermore, overexpression of miR-145 and miR-133a inhibited cellular proliferation, migration, and invasion, while promoted apoptosis in HCC cells. On the contrary, inhibition of miR-145 and miR-133a promoted cellular proliferation, migration, and invasion, while suppressed apoptosis in HCC cells.

Conclusion

Our study suggests that the abnormal upregulation of FSCN1 in HCC is associated with downregulation of miR-145 and miR-133a, and miR-145 and miR-133a inhibit malignant progression of HCC in vitro, possibly via directly targeting FSCN1.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Chiba T, Marusawa H, Ushijima T. Inflammation-associated cancer development in digestive organs: mechanisms and roles for genetic and epigenetic modulation. Gastroenterology. 2012;143:550–563.

    Article  CAS  PubMed  Google Scholar 

  2. Shlomai A, de Jong YP, Rice CM. Virus associated malignancies: the role of viral hepatitis in hepatocellular carcinoma. Semin Cancer Biol. 2014;26:78–88.

    Article  CAS  PubMed  Google Scholar 

  3. Pang RW, Poon RT. Cancer stem cell as a potential therapeutic target in hepatocellular carcinoma. Curr Cancer Drug Targets. 2012;12:1081–1094.

    CAS  PubMed  Google Scholar 

  4. Wang XW, Heegaard NH, Orum H. MicroRNAs in liver disease. Gastroenterology. 2012;142:1431–1443.

    Article  CAS  PubMed  Google Scholar 

  5. Borel F, Konstantinova P, Jansen PL. Diagnostic and therapeutic potential of miRNA signatures in patients with hepatocellular carcinoma. J Hepatol. 2012;56:1371–1383.

    Article  CAS  PubMed  Google Scholar 

  6. Wang Z, Zhang X, Yang Z, et al. MiR-145 regulates PAK4 via the MAPK pathway and exhibits an antitumor effect in human colon cells. Biochem Biophys Res Commun. 2012;427:444–449.

    Article  CAS  PubMed  Google Scholar 

  7. Zheng L, Pu J, Qi T, et al. miRNA-145 targets v-ets erythroblastosis virus E26 oncogene homolog 1 to suppress the invasion, metastasis, and angiogenesis of gastric cancer cells. Mol Cancer Res. 2013;11:182–193.

    Article  CAS  PubMed  Google Scholar 

  8. Noh JH, Chang YG, Kim MG, et al. MiR-145 functions as a tumor suppressor by directly targeting histone deacetylase 2 in liver cancer. Cancer Lett. 2013;335:455–462.

    Article  CAS  PubMed  Google Scholar 

  9. Sperveslage J, Hoffmeister M, Henopp T, et al. Establishment of robust controls for the normalization of miRNA expression in neuroendocrine tumors of the ileum and pancreas. Endocrine. 2014;46:226–230.

    Article  CAS  PubMed  Google Scholar 

  10. Wong TS, Liu XB, Chung-Wai HA, et al. Identification of pyruvate kinase type M2 as potential oncoprotein in squamous cell carcinoma of tongue through microRNA profiling. Int J Cancer. 2008;123:251–257.

    Article  CAS  PubMed  Google Scholar 

  11. Datta J, Kutay H, Nasser MW, et al. Methylation mediated silencing of MicroRNA-1 gene and its role in hepatocellular carcinogenesis. Cancer Res. 2008;68:5049–5058.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Nasser MW, Datta J, Nuovo G, et al. Down-regulation of micro-RNA-1 (miR-1) in lung cancer. Suppression of tumorigenic property of lung cancer cells and their sensitization to doxorubicin-induced apoptosis by miR-1. J Biol Chem. 2008;283:33394–33405.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Hashimoto Y, Skacel M, Adams JC. Roles of fascin in human carcinoma motility and signaling: prospects for a novel biomarker? Int J Biochem Cell Biol. 2005;37:1787–1804.

    Article  CAS  PubMed  Google Scholar 

  14. Li A, Dawson JC, Forero-Vargas M, et al. The actin-bundling protein fascin stabilizes actin in invadopodia and potentiates protrusive invasion. Curr Biol. 2010;20:339–345.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Chan C, Jankova L, Fung CL, et al. Fascin expression predicts survival after potentially curative resection of node-positive colon cancer. Am J Surg Pathol. 2010;34:656–666.

    PubMed  Google Scholar 

  16. Fu H, Hu Z, Wen J, et al. TGF-beta promotes invasion and metastasis of gastric cancer cells by increasing fascin1 expression via ERK and JNK signal pathways. Acta Biochim Biophys Sin. 2009;41:648–656.

    Article  CAS  PubMed  Google Scholar 

  17. Vignjevic D, Kojima S, Aratyn Y, et al. Role of fascin in filopodial protrusion. J Cell Biol. 2006;174:863–875.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Li A, Dawson JC, Forero-Vargas M, et al. The actin-bundling protein fascin stabilizes actin in invadopodia and potentiates protrusive invasion. Curr Biol. 2010;20:339–345.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Machesky LM, Li A. Fascin: invasive filopodia promoting metastasis. Commun Integr Biol. 2010;3:263–270.

    Article  PubMed Central  PubMed  Google Scholar 

  20. Wen YH, Yee H, Goswami S, et al. Fascin expression in serous tumors of ovary correlates with aggressiveness of malignancy. Int J Gynecol Pathol. 2009;28:187–192.

    Article  PubMed  Google Scholar 

  21. Iguchi T, Aishima S, Umeda K, et al. Fascin expression in progression and prognosis of hepatocellular carcinoma. J Surg Oncol. 2009;100:575–579.

    Article  PubMed  Google Scholar 

  22. Hayashi Y, Osanai M, Lee GH. Fascin-1 expression correlates with repression of E-cadherin expression in hepatocellular carcinoma cells and augments their invasiveness in combination with matrix metalloproteinases. Cancer Sci. 2011;102:1228–1235.

    Article  CAS  PubMed  Google Scholar 

  23. Xu Q, Liu LZ, Qian X, et al. MiR-145 directly targets p70S6K1 in cancer cells to inhibit tumor growth and angiogenesis. Nucleic Acids Res. 2012;40:761–774.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. Spizzo R, Nicoloso MS, Lupini L, et al. miR-145 participates with TP53 in a death-promoting regulatory loop and targets estrogen receptor-alpha in human breast cancer cells. Cell Death Differ. 2010;17:246–254.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Wang Y, Hu C, Cheng J, et al. MicroRNA-145 suppresses hepatocellular carcinoma by targeting IRS1 and its downstream Akt signaling. Biochem Biophys Res Commun. 2014;446:1255–1260.

    Article  CAS  PubMed  Google Scholar 

  26. Akanuma N, Hoshino I, Akutsu Y, et al. MicroRNA-133a regulates the mRNAs of two invadopodia-related proteins, FSCN1 and MMP14, in esophageal cancer. Br J Cancer. 2014;110:189–198.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Wu ZS, Wang CQ, Xiang R, et al. Loss of miR-133a expression associated with poor survival of breast cancer and restoration of miR-133a expression inhibited breast cancer cell growth and invasion. BMC Cancer. 2012;12:51.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Chiyomaru T, Enokida H, Tatarano S, et al. miR-145 and miR-133a function as tumour suppressors and directly regulate FSCN1 expression in bladder cancer. Br J Cancer. 2010;102:883–891.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Kano M, Seki N, Kikkawa N, et al. miR-145, miR-133a and miR-133b: tumor-suppressive miRNAs target FSCN1 in esophageal squamous cell carcinoma. Int J Cancer. 2010;127:2804–2814.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by the National Natural Science Funds (51305464, 51290295) and University Teachers Freedom to Explore Funding of Central South University (2012QNZT166).

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Centre of Experimental Medicine, Third Xiangya Hospital of Central South University, Changsha, 410013, Hunan, China

    Guohui Wang & Shaihong Zhu

  2. Department of Pathology, Third Xiangya Hospital of Central South University, No. 138 Tongzipo Road, Changsha, 410013, Hunan, China

    Yonghong Gu, Qian Chen, Xinrong Liu & Hua Fu

Authors
  1. Guohui Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shaihong Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yonghong Gu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Qian Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xinrong Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hua Fu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hua Fu.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, G., Zhu, S., Gu, Y. et al. MicroRNA-145 and MicroRNA-133a Inhibited Proliferation, Migration, and Invasion, While Promoted Apoptosis in Hepatocellular Carcinoma Cells Via Targeting FSCN1. Dig Dis Sci 60, 3044–3052 (2015). https://doi.org/10.1007/s10620-015-3706-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-015-3706-9

Keywords

Search

Navigation