Abstract
MicroRNAs are a class of non-coding RNAs that function as key regulators of gene expression at the post-transcriptional level. In our previous research, we found that miR-23a was significantly up-regulated in human gastric adenocarcinoma cells. In the current study, we demonstrate that miR-23a suppresses paclitaxel-induced apoptosis and promotes the cell proliferation and colony formation ability of gastric adenocarcinoma cells. We have identified tumor suppressor interferon regulator factor 1 (IRF1) as a direct target gene of miR-23a. We performed a fluorescent reporter assay to confirm that miR-23a bound to the IRF1 mRNA 3′UTR directly and specifically. The ectopic expression of IRF1 markedly promoted paclitaxel-induced apoptosis and inhibited cell viability and colony formation ability, whereas the knockdown of IRF1 had the opposite effects. The restoration of IRF1 expression counteracted the effects of miR-23a on the paclitaxel-induced apoptosis and cell proliferation of gastric adenocarcinoma cells. Quantitative real-time PCR showed that miR-23a is frequently up-regulated in gastric adenocarcinoma tissues, whereas IRF1 is down-regulated in cancer tissues. Altogether, these results indicate that miR-23a suppresses paclitaxel-induced apoptosis and promotes cell viability and the colony formation ability of gastric adenocarcinoma cells by targeting IRF1 at the post-transcriptional level.
Highlights
Gastric cancer is a disease that is associated with a poor prognosis and a high mortality rate [1,2]
Human gastric adenocarcinoma cells were transfected with pcDNA3, pri-miR-23a, antisense oligonucleotide for miR-23a (ASO-23a) or ASO-NC
The loss of heterozygosity (LOH) observed in human gastric cancer strongly suggests the existence of tumor suppressor genes at the concerned locus
Summary
Gastric cancer is a disease that is associated with a poor prognosis and a high mortality rate [1,2]. Gastric cancer is the second leading cause of cancer death worldwide after lung cancer [3]. 90% of gastric cancers are adenocarcinomas, which originate from the glandular epithelium of the gastric mucosa [4]. Previous studies have suggested that gastric adenocarcinoma is a multifactorial disease [5]. Numerous studies have revealed that oncogenes or tumor suppressors may play important roles in the tumorigenesis and progression of gastric cancer [6,7]. The molecular mechanisms of gastric cancer development and progression remain unresolved
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have