Abstract
MicroRNA has been recently recognized as playing a prominent role in tumorigenesis and metastasis. Here, we report that miR-338-3p was epigenetically silenced in gastric cancer, and its down-regulation was significantly correlated with gastric cancer clinicopathological features. Strikingly, restoring miR-338-3p expression in SGC-7901 gastric cancer cells inhibited proliferation, migration, invasion and tumorigenicity in vitro and in vivo, at least partly through inducing apoptosis. Furthermore, we demonstrate the oncogene SSX2IP is a target of miR-338-3p. We propose that miR-338-3p functions as a tumor suppressor in gastric cancer, and the methylation status of its CpG island could serve as a potential diagnostic marker for gastric cancer.
Highlights
Gastric cancer is a malignancy with high incidence and the second leading cause of cancer death worldwide [1]
MicroRNA microarray was performed to detect the miRNA profiles in gastric cancer, and we found that miR-338-3p was significantly down-regulated. miR-338-3p, located at chromosome 17q25.3 with a length of 22 nt, was first reported in prion-induced neurodegeneration as the expression of miR-338-3p is reduced in the brains of mice infected with mouseadapted scrape [16]. miR-338-3p could regulate the mRNA level of its host gene Apoptosis-associated Tyrosine Kinase (AATK) in rat neurons [17]
Based on the idea that miR-338-3p serves as a tumor suppressor of GC, we further explored its effects on cell migration and invasion, a critical determinate of malignant progression and metastasis
Summary
Gastric cancer is a malignancy with high incidence and the second leading cause of cancer death worldwide [1]. It is of great significance to carry out in-depth study on the pathogenesis of gastric cancer and to look for new molecular makers and therapeutic targets. Multiple studies have revealed significant difference of microRNAs expression profiling between tumor cells and cells derived from normal tissues, indicating that microRNAs have played important roles in tumorigenesis [3,4]. Abnormal expression of microRNAs in tissues or serum is closely related to multiple human malignancies including gastric cancer [7,8], and several down-regulated microRNAs in gastric cancer tissues have tumor suppressing functions. MiR-15b, miR-16 and miR-21 etc have been connected to the development and clinical diagnosis of gastric cancer [11,12]. Our group has reported the anticancer role of miR-126, miR-409-3p and miR155 in gastric cancer [13,14,15]
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