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Article

Depletion of histone deacetylase 1 inhibits metastatic abilities of gastric cancer cells by regulating the miR-34a/CD44 pathway

  • Authors:
    • Lele Lin
    • Hongpeng Jiang
    • Mingkui Huang
    • Xu Hou
    • Xuepu Sun
    • Xian Jiang
    • Xuesong Dong
    • Xueying Sun
    • Baoguo Zhou
    • Haiquan Qiao
  • View Affiliations / Copyright

    Affiliations: Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China
  • Pages: 663-672
    |
    Published online on: May 28, 2015
       https://doi.org/10.3892/or.2015.4010
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Abstract

Overexpression of histone deacetylases (HDACs) is associated with higher metastatic rates and a poor prognosis in gastric cancer. However, the underlying mechanisms involved remain unclear. The present study aimed to investigate the molecular pathways that are involved in HDAC1-mediated metastatic activities in gastric cancer cells. First we used a microRNA (miRNA or miR) microarray to screen potential miRNAs whose expression can be altered by HDAC1 depletion. Of these miRNAs, miR-34a is important as it is often inactivated in cancer cells and acts as a tumor suppressor for various types of cancer. The reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) results confirmed that miR-34a was upregulated by HDAC1 knockdown. Cells depleted of HDAC1 had lower abilities to migrate, invade and adhere, which were restored by a miR-34a antagomiR. Depletion of HDAC1 also resulted in impaired microfilaments and microtubules, while co-transfection of the miR-34a antagomiR attenuated these changes in the cellular cytoskeleton. The HDAC1/miR-34a axis regulated the expression and activation of CD44 and its downstream factors including Bcl-2, Ras homolog family member A (RhoA), LIM domain kinase 1 (LIMK-1) and matrix metalloproteinase (MMP)-2. The latter three proteins were responsible for the organization of tubulin and actin cytoskeleton and the formation of cellular pseudopodia. In conclusion, results of the present study indicated that HDAC1 depletion inhibits the metastatic abilities of gastric cancer cells by regulating the miRNA-34a/CD44 pathway, which may be a potential target for the treatment of gastric cancer.
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1 

Siegel R, Naishadham D and Jemal A: Cancer statistics, 2013. CA Cancer J Clin. 63:11–30. 2013. View Article : Google Scholar : PubMed/NCBI

2 

Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV and Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 325:834–840. 2009. View Article : Google Scholar : PubMed/NCBI

3 

Venugopal B and Evans TR: Developing histone deacetylase inhibitors as anti-cancer therapeutics. Curr Med Chem. 18:1658–1671. 2011. View Article : Google Scholar : PubMed/NCBI

4 

Dovey OM, Foster CT and Cowley SM: Histone deacetylase 1 (HDAC1), but not HDAC2, controls embryonic stem cell differentiation. Proc Natl Acad Sci USA. 107:8242–8247. 2010. View Article : Google Scholar : PubMed/NCBI

5 

Delcuve GP, Khan DH and Davie JR: Targeting class I histone deacetylases in cancer therapy. Expert Opin Ther Targets. 17:29–41. 2013. View Article : Google Scholar

6 

Weichert W, Röske A, Gekeler V, Beckers T, Ebert MP, Pross M, Dietel M, Denkert C and Röcken C: Association of patterns of class I histone deacetylase expression with patient prognosis in gastric cancer: A retrospective analysis. Lancet Oncol. 9:139–148. 2008. View Article : Google Scholar : PubMed/NCBI

7 

Wang JC, Kafeel MI, Avezbakiyev B, Chen C, Sun Y, Rathnasabapathy C, Kalavar M, He Z, Burton J and Lichter S: Histone deacetylase in chronic lymphocytic leukemia. Oncology. 81:325–329. 2011. View Article : Google Scholar

8 

Li T, Lu YY, Zhao XD, Guo HQ, Liu CH, Li H, Zhou L, Han YN, Wu KC, Nie YZ, et al: MicroRNA-296–5p increases proliferation in gastric cancer through repression of Caudal-related homeobox 1. Oncogene. 33:783–793. 2014. View Article : Google Scholar

9 

Garzon R, Marcucci G and Croce CM: Targeting microRNAs in cancer: Rationale, strategies and challenges. Nat Rev Drug Discov. 9:775–789. 2010. View Article : Google Scholar : PubMed/NCBI

10 

Hermeking H: The miR-34 family in cancer and apoptosis. Cell Death Differ. 17:193–199. 2010. View Article : Google Scholar

11 

Buurman R, Gürlevik E, Schäffer V, Eilers M, Sandbothe M, Kreipe H, Wilkens L, Schlegelberger B, Kühnel F and Skawran B: Histone deacetylases activate hepatocyte growth factor signaling by repressing microRNA-449 in hepatocellular carcinoma cells. Gastroenterology. 143:811–20.e1. 152012. View Article : Google Scholar : PubMed/NCBI

12 

Wang Y, Toh HC, Chow P, Chung AY, Meyers DJ, Cole PA, Ooi LL and Lee CG: MicroRNA-224 is up-regulated in hepatocellular carcinoma through epigenetic mechanisms. FASEB J. 26:3032–3041. 2012. View Article : Google Scholar : PubMed/NCBI

13 

Mims A, Walker AR, Huang X, Sun J, Wang H, Santhanam R, Dorrance AM, Walker C, Hoellerbauer P, Tarighat SS, et al: Increased anti-leukemic activity of decitabine via AR-42-induced upregulation of miR-29b: A novel epigenetic-targeting approach in acute myeloid leukemia. Leukemia. 27:871–878. 2013. View Article : Google Scholar :

14 

Chakraborty S, Mazumdar M, Mukherjee S, Bhattacharjee P, Adhikary A, Manna A, Chakraborty S, Khan P, Sen A and Das T: Restoration of p53/miR-34a regulatory axis decreases survival advantage and ensures Bax-dependent apoptosis of non-small cell lung carcinoma cells. FEBS Lett. 588:549–559. 2014. View Article : Google Scholar : PubMed/NCBI

15 

LeBoeuf M, Terrell A, Trivedi S, Sinha S, Epstein JA, Olson EN, Morrisey EE and Millar SE: Hdac1 and Hdac2 act redundantly to control p63 and p53 functions in epidermal progenitor cells. Dev Cell. 19:807–818. 2010. View Article : Google Scholar : PubMed/NCBI

16 

Zhai B, Hu F, Jiang X, Xu J, Zhao D, Liu B, Pan S, Dong X, Tan G, Wei Z, et al: Inhibition of Akt reverses the acquired resistance to sorafenib by switching protective autophagy to autophagic cell death in hepatocellular carcinoma. Mol Cancer Ther. 13:1589–1598. 2014. View Article : Google Scholar : PubMed/NCBI

17 

Zhao D, Zhai B, He C, Tan G, Jiang X, Pan S, Dong X, Wei Z, Ma L, Qiao H, et al: Upregulation of HIF-2α induced by sorafenib contributes to the resistance by activating the TGF-α/EGFR pathway in hepatocellular carcinoma cells. Cell Signal. 26:1030–1039. 2014. View Article : Google Scholar : PubMed/NCBI

18 

Wei Z, Jiang X, Liu F, Qiao H, Zhou B, Zhai B, Zhang L, Zhang X, Han L, Jiang H, et al: Downregulation of Skp2 inhibits the growth and metastasis of gastric cancer cells in vitro and in vivo. Tumour Biol. 34:181–192. 2013. View Article : Google Scholar

19 

Naor D, Nedvetzki S, Golan I, Melnik L and Faitelson Y: CD44 in cancer. Crit Rev Clin Lab Sci. 39:527–579. 2002. View Article : Google Scholar : PubMed/NCBI

20 

Scott GK, Mattie MD, Berger CE, Benz SC and Benz CC: Rapid alteration of microRNA levels by histone deacetylase inhibition. Cancer Res. 66:1277–1281. 2006. View Article : Google Scholar : PubMed/NCBI

21 

Izzotti A, Cartiglia C, Steele VE and De Flora S: MicroRNAs as targets for dietary and pharmacological inhibitors of mutagenesis and carcinogenesis. Mutat Res. 751:287–303. 2012. View Article : Google Scholar : PubMed/NCBI

22 

Zhao J, Lammers P, Torrance CJ and Bader AG: TP53-independent function of miR-34a via HDAC1 and p21CIP1/WAF1. Mol Ther. 21:1678–1686. 2013. View Article : Google Scholar : PubMed/NCBI

23 

Nalls D, Tang SN, Rodova M, Srivastava RK and Shankar S: Targeting epigenetic regulation of miR-34a for treatment of pancreatic cancer by inhibition of pancreatic cancer stem cells. PLoS One. 6:e240992011. View Article : Google Scholar : PubMed/NCBI

24 

Zeng SS, Yamashita T, Kondo M, Nio K, Hayashi T, Hara Y, Nomura Y, Yoshida M, Hayashi T, Oishi N, et al: The transcription factor SALL4 regulates stemness of EpCAM-positive hepatocellular carcinoma. J Hepatol. 60:127–134. 2014. View Article : Google Scholar

25 

Liu C, Kelnar K, Liu B, Chen X, Calhoun-Davis T, Li H, Patrawala L, Yan H, Jeter C, Honorio S, et al: The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44. Nat Med. 17:211–215. 2011. View Article : Google Scholar : PubMed/NCBI

26 

Zhang Y, Xia H, Ge X, Chen Q, Yuan D, Chen Q, Leng W, Chen L, Tang Q and Bi F: CD44 acts through RhoA to regulate YAP signaling. Cell Signal. 26:2504–2513. 2014. View Article : Google Scholar : PubMed/NCBI

27 

Zöller M: CD44: Can a cancer-initiating cell profit from an abundantly expressed molecule? Nat Rev Cancer. 11:254–267. 2011. View Article : Google Scholar : PubMed/NCBI

28 

Sumoza-Toledo A and Santos-Argumedo L: The spreading of B lymphocytes induced by CD44 cross-linking requires actin, tubulin, and vimentin rearrangements. J Leukoc Biol. 75:233–239. 2004. View Article : Google Scholar

29 

Lin MT, Lin BR, Chang CC, Chu CY, Su HJ, Chen ST, Jeng YM and Kuo ML: IL-6 induces AGS gastric cancer cell invasion via activation of the c-Src/RhoA/ROCK signaling pathway. Int J Cancer. 120:2600–2608. 2007. View Article : Google Scholar : PubMed/NCBI

30 

McConnell BV, Koto K and Gutierrez-Hartmann A: Nuclear and cytoplasmic LIMK1 enhances human breast cancer progression. Mol Cancer. 10:752011. View Article : Google Scholar : PubMed/NCBI

31 

Murphy G and Nagase H: Progress in matrix metalloproteinase research. Mol Aspects Med. 29:290–308. 2008. View Article : Google Scholar : PubMed/NCBI

32 

Hanna S and El-Sibai M: Signaling networks of Rho GTPases in cell motility. Cell Signal. 25:1955–1961. 2013. View Article : Google Scholar : PubMed/NCBI

33 

Struckhoff AP, Rana MK and Worthylake RA: RhoA can lead the way in tumor cell invasion and metastasis. Front Biosci. 16:1915–1926. 2011. View Article : Google Scholar

34 

Kim Y, Lee YS, Choe J, Lee H, Kim YM and Jeoung D: CD44-epidermal growth factor receptor interaction mediates hyaluronic acid-promoted cell motility by activating protein kinase C signaling involving Akt, Rac1, Phox, reactive oxygen species, focal adhesion kinase, and MMP-2. J Biol Chem. 283:22513–22528. 2008. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Lin L, Jiang H, Huang M, Hou X, Sun X, Jiang X, Dong X, Sun X, Zhou B, Qiao H, Qiao H, et al: Depletion of histone deacetylase 1 inhibits metastatic abilities of gastric cancer cells by regulating the miR-34a/CD44 pathway. Oncol Rep 34: 663-672, 2015.
APA
Lin, L., Jiang, H., Huang, M., Hou, X., Sun, X., Jiang, X. ... Qiao, H. (2015). Depletion of histone deacetylase 1 inhibits metastatic abilities of gastric cancer cells by regulating the miR-34a/CD44 pathway. Oncology Reports, 34, 663-672. https://doi.org/10.3892/or.2015.4010
MLA
Lin, L., Jiang, H., Huang, M., Hou, X., Sun, X., Jiang, X., Dong, X., Sun, X., Zhou, B., Qiao, H."Depletion of histone deacetylase 1 inhibits metastatic abilities of gastric cancer cells by regulating the miR-34a/CD44 pathway". Oncology Reports 34.2 (2015): 663-672.
Chicago
Lin, L., Jiang, H., Huang, M., Hou, X., Sun, X., Jiang, X., Dong, X., Sun, X., Zhou, B., Qiao, H."Depletion of histone deacetylase 1 inhibits metastatic abilities of gastric cancer cells by regulating the miR-34a/CD44 pathway". Oncology Reports 34, no. 2 (2015): 663-672. https://doi.org/10.3892/or.2015.4010
Copy and paste a formatted citation
x
Spandidos Publications style
Lin L, Jiang H, Huang M, Hou X, Sun X, Jiang X, Dong X, Sun X, Zhou B, Qiao H, Qiao H, et al: Depletion of histone deacetylase 1 inhibits metastatic abilities of gastric cancer cells by regulating the miR-34a/CD44 pathway. Oncol Rep 34: 663-672, 2015.
APA
Lin, L., Jiang, H., Huang, M., Hou, X., Sun, X., Jiang, X. ... Qiao, H. (2015). Depletion of histone deacetylase 1 inhibits metastatic abilities of gastric cancer cells by regulating the miR-34a/CD44 pathway. Oncology Reports, 34, 663-672. https://doi.org/10.3892/or.2015.4010
MLA
Lin, L., Jiang, H., Huang, M., Hou, X., Sun, X., Jiang, X., Dong, X., Sun, X., Zhou, B., Qiao, H."Depletion of histone deacetylase 1 inhibits metastatic abilities of gastric cancer cells by regulating the miR-34a/CD44 pathway". Oncology Reports 34.2 (2015): 663-672.
Chicago
Lin, L., Jiang, H., Huang, M., Hou, X., Sun, X., Jiang, X., Dong, X., Sun, X., Zhou, B., Qiao, H."Depletion of histone deacetylase 1 inhibits metastatic abilities of gastric cancer cells by regulating the miR-34a/CD44 pathway". Oncology Reports 34, no. 2 (2015): 663-672. https://doi.org/10.3892/or.2015.4010
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