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

  • Published online on: May 28, 2015     https://doi.org/10.3892/or.2015.4010
  • Pages: 663-672
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


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.
View Figures
View References

Related Articles

Journal Cover

August-2015
Volume 34 Issue 2

Print ISSN: 1021-335X
Online ISSN:1791-2431

Sign up for eToc alerts

Recommend to Library

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