Although a growing number of novel treatment strategies have been developed for HCC, such as molecular targeted therapy and gene therapy, to our disappointment, satisfactory therapeutic outcomes have not been achieved [
21,
22]. Considering that the survival rate of HCC is still low, further identification of new prognostic markers remains important for the prevention and treatment of HCC.
The discovery that noncoding components of the genome, including microRNA, can contribute to the pathogenesis of cancer has led investigators to contemplate using these molecules to guide clinical decision making [
23]. So far, there are more than 1000 microRNAs annotated by the latest version of miRBase. The expression of miRNAs is remarkably deregulated in HCC, strongly suggesting that miRNAs are involved in the initiation and progression of this disease. MiR-25 is a member of the miR-106b~25 cluster, which includes miR-106b, miR-93 and miR-25, that is located within intron 13 of the minichromosome maintenance protein 7 (MCM7) gene on chromosome 7q22.1 [
14]. Previous studies have shown that the expression of miR-25 was up-regulated significantly in human stomach cancer, ovarian cancer, and prostate cancer [
16‐
18]. In the study by Kim BH et al., miR-25 was found to be up-regulated in human gastric carcinoma tissues when compared to adjacent non-neoplastic tissues. The high expression of miR-25 in gastric carcinoma tissues may be a high risk factor associated with tumor penetration through serosa, lymph node metastasis, distant metastasis, and poor long-term survival in patients undergoing radical resection and adjuvant systemic chemotherapy [
16]. Poliseno L et al. found that miR-106b~25 cluster was aberrantly overexpressed in human prostate cancer, which potentiated cellular transformation both in vitro and in vivo. They demonstrated that the intronic miR-106b~25cluster cooperated with its host gene MCM7 in cellular transformation both in vitro and in vivo [
17]. Zhang H et al. have found that miR-25 was strongly up-regulated in ovarian cancer tissue versus adjacent non-tumor tissue. The expression levels of miR-25 in ovarian cancer cell lines were similar with ovarian cancer samples compared with the normal ovarian epithelial cells. Overexpression of miR-25 in ovarian cancer cells enhanced cell proliferation whereas down-regulation of miR-25 induced apoptosis. The effects of miR-25 abrogation were partly mediated by the intrinsic apoptosis pathway. Many pro-apoptotic proteins such as Bim, Bax and caspase-3 were up-regulated after transfection [
18]. However, investigators also found that expression of miR-25 was down-regulated in other cancer. Li Q et al. found that the expression of miR-25 was down-regulated in colon cancer, and miR-25 might suppress the proliferation and migration of colon cancer cells as a tumor suppressor gene in vitro and in vivo [
24]. Therefore, we speculate that the function of miR-25 is tissue specific.
Li Y et al. have found that miR-25 was strongly up-regulated in HCC tissue when compared with the corresponding paired non-tumor samples. However, the clinical significance of miR-25 gene expression in HCC remains unclear. In the present study, we found that miR-25 expression was proven to be associated with advanced TNM stage, suggesting that miR-25 might be involved in the carcinogenesis and metastasis of HCC. More importantly, we proved that patients with a high expression of miR-25 tended to have shorter survival than patients with lower levels, indicating that high miR-25 level is a marker of poor prognosis for patients with HCC. However, the precise molecular mechanisms behind the altered expression of miR-25 in HCC and its function are not very clear. In the study by Li Y et al., knock-down studies for the miR-106b-25cluster, which includes miR-106b, miR-93 and miR-25, showed that the expression of the cluster was necessary for cell proliferation and for anchorage independent growth [
19]. Additional studies are needed to more clearly and comprehensively articulate the molecular mechanisms of both the cause and the effects of altered expression of miR-25 in the development and/or progression of HCC.
In summary, to the best of our knowledge, the present study is the first to report the differential expression of miR-25 in HCC and the possible use of miR-25 as a novel prognostic marker in HCC. The present findings demonstrate high expression of miR-25 in HCC tissue, which is associated with a poor prognosis in HCC patients. Further studies are needed to elucidate the mechanisms of action of miR-25 in HCC.