Abstract
Overcoming chemorestistance to 5-fluorouracil (5-FU) could offer a new treatment option for highly malignant colon cancer. In our study, differential microRNA expression profiling revealed that miR-214 is downregulated in 5-FU-resistant colon cancer cells compared to normal cells. In vitro, miR-214 could sensitize non-resistant colon cancer cells and 5-FU-resistant colon cancer cellsto 5-FU. Functionally, miR-214 inhibited cell clone formation and cell growth and enhanced 5-FU-inducing cell apoptosis and caspase-3 levels. MiR-214 targeted heat shock protein 27 (Hsp27), as confirmed via dual luciferase reporter assays and western blots. Hsp27 also sensitized HT-29 and LoVo to 5-FU by enhancing cell apoptosis. Overexpression of Hsp27 could block miR-214 with an effect on the sensitivity of colon cancer cells to 5-FU. In conclusion, miR-214 sensitizes colon cancer cells to 5-FU by targeting Hsp27, indicating a significant role for this miRNA in colon cancer chemotherapy.
Highlights
MicroRNAs are a class of endogenous, small noncoding RNAs that negatively regulate target gene expression by binding to the 3′-untranslated region (3’UTR) of mRNAs for translational repression or degradation [1, 2]
The miRNA expression profile revealed that miR-214 was downregulated in 5-FU-resistant cells compared to parental cells (Fig. 1b and c)
In HT-29 and LoVo cells, inhibition of miR-214 bytransfection with miRNA antisense oligonucleotides (ASO) reduced the cell growth inhibition by 5-FU and enhanced the 50% inhibitory concentration (IC50) of the cells (Fig. 1d and e).In HT-29/5-FU and LoVo/5-FU, overexpression of miR-214 by transfection with miR-214 mimics enhanced the cell growth inhibition of 5-FU and reduced the IC50 of cells (Fig. 1f and g; p < 0.05).These results indicated that miR-214 sensitized the colon cancer cells to 5-FU
Summary
MicroRNAs (miRNA or miRs) are a class of endogenous, small noncoding RNAs that negatively regulate target gene expression by binding to the 3′-untranslated region (3’UTR) of mRNAs for translational repression or degradation [1, 2]. Previous studies have revealed that miRNAs are involved in various cellular processes, including cell growth, development and apoptosis, and in the chemotherapy response [3]. Recent studies have shown that it functions as a tumor suppressor in human colon cancer [6, 7] and can bind to the3’UTR of ARL2. MiR-214 can target Necl-2 and regulate ErbB2/ErbB3 signaling [8]. Chemotherapy resistance is a major factor in the treatment difficulty of this cancer type. If resistance to the chemotherapeutic 5-fluorouracil (5-FU) could be overcome, it would give another promosing option for treating this highly malignant cancer
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
