Affiliations: [a] The First Hospital of Qinhuangdao, Hebei, China | [b] The Health Supervision Institude of Haigang District Qinhuangdao, Hebei, China
Correspondence:
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Corresponding author: Yunsheng Guo, The First Hospital of Qinhuangdao, Hebei, China. E-mail:yunsheng_guo08@163.com
Abstract: The mechanisms underlying oxaliplatin (OXA) resistance in colon cancer cells
are not fully understood. MicroRNAs (miRNAs) play important roles in
tumorigenesis and drug resistance. However, the relationship between miRNA
and OXA resistance in colon cancer cells has not been previously explored.
In this study, we utilized microRNA microarray analysis and real-time PCR to
verify that miR-93, miR-191, miR-137, miR-181 and miR-491-3p were
significantly down-regulated and that miR-96, miR-21, miR-22, miR-15b and
miR-92 were up-regulated in both HCT-15/OXA and SW480/OXA cell lines.
Blocking miR-137 caused a significant inhibition of OXA-induced cytotoxicity,
therefore, miR-137 was chosen for further research. An in vitro cell
viability assay showed that knockdown of miR-137 in HCT-15 and SW480 cells
caused a marked inhibition of OXA-induced cytotoxicity. Moreover, we found
that miR-137 was involved in repression of YBX1 expression through targeting
its 3'-untranslated region. Furthermore, down-regulation of miR-137
conferred OXA resistance in parental cells, while over-expression of miR-137
sensitized resistant cells to OXA, which was partly rescued by YBX1 siRNA.
The results of this study may aid the development of therapeutic strategies
to overcome colon cancer cell resistance to OXA.
Keywords: Colon cancer, miR-137, YBX1, drug resistance
