%0 Journal Article
%T Upregulated microRNAİ\193aİ\3p is responsible for cisplatin resistance in CD44(+) gastric cancer cells
%A Dayeon Yu
%A Do Y. Lee
%A Hyunİ\Soo Shin
%A Jeongİ\Hyeon Jo
%A So D. Lee
%A Yong C. Lee
%J Archive of "Cancer Science".
%D 2019
%R 10.1111/cas.13894
%X Cisplatin is a wellİ\known anticancer drug used to treat various cancers. However, development of cisplatin resistance has hindered the efficiency of this drug in cancer treatment. Development of chemoresistance is known to involve many signaling pathways. Recent attention has focused on microRNAs (miRNAs) as potentially important upstream regulators in the development of chemoresistance. CD44 is one of the gastric cancer stem cell markers and plays a role in regulating selfİ\renewal, tumor initiation, metastasis and chemoresistance. The purpose of the present study was to examine the mechanism of miRNAİ\mediated chemoresistance to cisplatin in CD44İ\positive gastric cancer stem cells. We sorted gastric cancer cells according to level of CD44 expression by FACS and analyzed their miRNA expression profiles by microarray analysis. We found that miRİ\193aİ\3p was significantly upregulated in CD44(+) cells compared with CD44(£ż) cells. Moreover, SRSF2 of miRİ\193aİ\3p target gene was downregulated in CD44(+) cells. We studied the modulation of Bclİ\X and caspase 9 mRNA splicing by SRSF2 and found that more proİ\apoptotic variants of these genes were generated. We also found that downstream antiİ\apoptotic genes such as Bclİ\2 were upregulated, whereas proİ\apoptotic genes such as Bax and cytochrome C were downregulated in CD44(+) cells compared to CD44(£ż) cells. In addition, we found that an elevated level of miRİ\193aİ\3p triggered the development of cisplatin resistance in CD44(+) cells. Inhibition of miRİ\193aİ\3p in CD44(+) cells increased SRSF2 expression and also altered the levels of multiple apoptotic genes. Furthermore, inhibition of miRİ\193aİ\3p reduced cell viability and increased the number of apoptotic cells. Therefore, miRİ\193aİ\3p may be implicated in the development of cisplatin resistance through regulation of the mitochondrial apoptosis pathway. miRİ\193aİ\3p could be a promising target for cancer therapy in cisplatinİ\resistant gastric cancer
%K apoptosis
%K cancer
%K CD44(+) cell
%K cisplatin
%K miRİ\193aİ\3p
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361556/