In:
Cellular Physiology and Biochemistry, S. Karger AG, Vol. 50, No. 2 ( 2018), p. 411-425
Abstract:
Background/Aims: MicroRNAs (miRNAs) have been well studied in human carcinogenesis and cancer progression. Our previous study showed the down-regulation of miR-338-3p expression in human gastric cancer (GC). However, the reasons of this dysregulation remain largely unclear. Methods: Bisulfite sequence analysis was performed to explore the methylation status of the promoter region of miR-338-3p. Cell wound-healing and transwell assays were performed to examine the capacity of cell migration and cell interaction. A dual-luciferase reporter was used to validate the bioinformatics-predicted target gene of miR-338-3p. Western blotting, RNA interference, and immunofluorescence (IF) were used to evaluate the expression of MMPs and the location of N-cadherin to determine the mechanism underlying miR-338-3p-induced anti-tumor effects. Results: miR-338-3p was epigenetically silenced, and this loss of expression was significantly correlated with the Borrmann Stage in GC. Restoring miR-338-3p expression in BGC-823 cells inhibited cell migration and invasion. Moreover, Ras-related protein (Rab-14) and Hedgehog acyltransferase (Hhat) were identified as direct targets of miR-338-3p. Both enforced expression of miR-338-3p and small interfering RNA induced Rab14-mediated accumulation of N-cadherin in the cell -cell junctions or Hhat-associated matrix metalloproteinase (MMP) degradation, which may underline the metastasis defects caused by loss of miR-338-3p in GC. Conclusion: These data indicate that miR-338-3p functions as a tumor suppressor in GC, and that the hypermethylation status of its CpG island might be a novel potential strategy for treating GC.
Type of Medium:
Online Resource
ISSN:
1015-8987
,
1421-9778
Language:
English
Publisher:
S. Karger AG
Publication Date:
2018
detail.hit.zdb_id:
1482056-0
SSG:
12
SSG:
15,3
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