| One of the major obstacles in the treatment of cancer is resistance to standard
chemotherapeutic drugs. According to the numerous reports, miR‐200c is involved in
many cancers, especially gastric cancer, and also miR‐200c has been known as an
effective factor in the elimination of chemotherapy resistance. The purpose of this
study was to explore the potential function and mechanism of miR‐200c and cisplatin
in the inhibition of migration and induction of apoptosis in gastric cancer cells. In this
study, first, miR‐200c mimics and LNA‐anti‐miR‐200c were transfected into KATOIII
cells. Moreover, 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay
results revealed that increased miR‐200c expression and cisplatin can more inhibited
the proliferation of KATOIII cells. MiR‐200c overexpression inhibited the movement
of KATOIII cells in wound healing assay. Subsequently, miR‐200c/cisplatin could
suppress colony formation in KATOIII cells. To identify a potential miR‐200c target,
we investigated the effect of miR‐200c modulation on RhoE, PTEN, VEGFR, and
MMP9 expression levels. Increased miR‐200c expression caused a reduction in
VEGFR and MMP9 mRNA and protein, suggesting that VEGFR and MMP9 are targets
of miR‐200c. In addition, reverse‐transcription polymerase chain reaction assays
showed that RhoE is target gene of miR‐200c and LNA‐anti‐miR‐200c suppressed the
expression of PTEN. Flow cytometry and 4′,6‐diamidino‐2‐phenylindole staining
analysis indicated that miR‐200c increased the cisplatin‐induced apoptosis which may
be associated with suppression of RhoE expression in KATOIII cells, also cell‐cycle
analysis showed the arrest of cell‐cycle progression at the G2 phase. These data
demonstrated that miR‐200c functioned as a suppressor gene in KATOIII cells. Also,
miR‐200c can be a potential therapeutic approach to overcome chemoresistance
during cisplatin chemotherapy. |