Affiliations: [a] Department of Emergency Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China | [b] Department of Gastroenterology, People's Hospital of Juxian, Rizhao, Shandong, China | [c] Department of General Surgery, The Second Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
Correspondence:
[*]
Corresponding author: Peng Gao, Department of Emergency Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China. E-mail:liuzmhcc@126.com
Abstract: BACKGROUND AND AIMS: Growing evidence suggests that microRNA plays
an essential role in the development and metastasis of many tumors,
including gastric cancer (GC). Expression of microRNA-203 (miR-203) has been
reported to decrease in GC. In addition, overexpression of miR-203
inhibits grow of GC cells in vitro and in vivo. However, whether miR-203
affects cell migration and invasion of GC remains unclear. This study aimed
to reveal the role of miR-203 on migration and invasion of GC, and its
potential mechanisms. METHODS: Synthetic pre-miR-203 (miR-203),
anti-miR-203 and scrambled negative control RNAs was transfected into the
gastric cancer SGC7901 cells to generate miR-203 or anti-miR-203-transfected
stable clones. The roles of miR-203 on cell invasion and motility were then
analyzed by Transwell migration assay and Wound healing assay in vitro.
Using siRNA to targeting ERK1/2, Slug, and E-cadherin or Slug cDNA
transfection (to increase Slug expression) to examine the miR-203 signaling
pathway. We also examined the efficacies of miR-203 or anti-miR-203 on
peritoneal metastasis of SGC7901 cells in the nude mouse model. RESULTS: Overexpression of miR-203
inhibits SGC7901 cell invasion and motility, followed by decreased
phospho-ERK1/2 (pERK1/2) and Slug expression, as well as increased E-cadherin
expression. Re-expression of Slug in miR-203/SGC7901cells decreased
E-cadherin expression and restored the invasive phenotypes. Targeting
E-cadherin in miR-203/SGC7901cells also restored the invasive phenotypes.
Inhibition of miR-203 promotes SGC7901 cell invasion and motility, followed
by increased phospho-ERK1/2 (pERK1/2) and Slug expression, as well as
decreased E-cadherin expression. Targeting ERK1/2 or Slug in
anti-miR-203/SGC7901cells increased E-cadherin expression and reversed the
invasive phenotypes. In addition, targeting ERK1/2 decreased Slug and
increased the E-cadherin expression. Significantly, we found that miR-203
could exert marked inhibition of the peritoneal metastasis of SGC7901 in
nude mice in vivo. Targeting miR-203 could exert marked promotion of the peritoneal
metastasis of SGC7901 in nude mice in vivo. CONCLUSIONS: miR-203/ERK1/2/Slug/E-cadherin signaling pathway plays an essential role
on SGC7901 cell invasion and motility. miR-203 can be novel modalities to
prevent peritoneal metastasis of invasive cancers such as gastric cancer.
