Accurate prediction of the prognosis for the individual patient with cervical cancer is of great importance, and molecular biomarkers that could be served as prognostic markers would be useful in determining an individualized treatment plan for a cervical cancer patient. However, the biomarkers used in this tumor group today are not satisfactory, and it is needed to exploit additional markers to fine-tune this process.
MiRNAs, a class of naturally occurring, non-coding, short single stranded RNAs, are deregulated in cancer, and they are involved in malignant transformation and tumor development. In recent years, numerous studies have shown aberrant expression of miRNAs in human cancers, including cervical cancer, some of which function as tumor suppressor genes or oncogenes. Due to their tissue-and disease-specific expression patterns and tremendous regulatory potential, miRNAs are being identified as diagnostic and prognostic biomarkers, as well as additional therapeutic tools [
16],[
17]. As more and more studies report the relationships between miRNAs and cervical cancer, its potential as novel biomarkers in cervical cancer is growing [
18]-[
20].
MiR-126, derived from a common precursor structure located within the epidermal growth factor-like domain 7 (EGFL7) gene, is frequently down-regulated in a variety of malignancies and acts as a potential tumor suppressor [
10]-[
12]. Previous studies have reported that miR-126 may play a role in tumorigenesis and growth by regulating the vascular endothelial growth factor (VEGF)/phosphoinositol 3-kinase (PI3K)/AKT signaling pathways in human breast cancer [
21]. Additionally, this miRNA may function as a tumor suppressor, with Crk as a direct target, in gastric cancer [
22] and via the regulation of ADAM9b in pancreatic cancer [
23]. miR-126 may also play a role in angiogenesis in ischemia [
24], and has also been reported to enhance the sensitivity of non-small cell lung cancer(NSCLC) cells to anticancer agents by targeting VEGF-A [
25]. Together, these previous studies have demonstrated the important role of miR-126 in various cancers. Moreover, low expression of miR-126 has been found to be correlated with poor prognosis in patients with breast cancer, adult T cell leukemia, CRC and malignant mesothelioma [
13]-[
15]. Previously, miR-126 expression in cervical cancer tissues was found to be significantly decreased compared with that in normal cervical tissues. Yu et al. found that miR-126 was able to suppress the proliferation of cervical cancer cells and alters cell sensitivity to the chemotherapeutic drug bleomycin [
26]. However, the clinical significance and prognostic value of miR-126 in cervical cancer have not been investigated. In the present study, we showed that miR-126 was significantly down-regulated in cervical cancer tissues for the first time. Decreased miR-126 expression in cervical cancer was found to be significantly associated with lymphatic invasion, distant metastasis, FIGO stage, and histological grade, suggesting that miR-126 might be involved in the carcinogenesis and metastasis of cervical cancer. More importantly, we proved that patients with a lower expression of miR-126 tended to have shorter survival than patients with higher levels. Furthermore, multivariate analysis revealed that miR-126 expression was independently associated with the OS, indicating that lower miR-126 level was a marker of poor prognosis for patients with cervical cancer.