Liver cancer (mostly hepatocellular carcinoma [HCC]) is the sixth most prevalent cancer worldwide [
1], and it is the second most frequent cause of cancer-related death in men and the sixth most frequent in women [
2]. Surgical resection provides a cure in only about 20–30 % of HCC patients, and the reported 5-year survival rate is 40–50 %, with a high incidence of postoperative recurrence [
3,
4]. Postoperative recurrence remains a major problem in reducing patient survival [
5], and it may occur because of intrahepatic metastasis from the original primary tumor even for the patients with early-stage cancer [
3] or from de novo carcinogenesis [
6]. The precise mechanisms involved in metastasis are still not well understood, but accumulating evidence suggests that an epithelial-mesenchymal transition (EMT)-like process plays a major role [
7]. EMT is a transient and reversible switch from a polarized and epithelial phenotype to a fibroblastoid or mesenchymal cellular phenotype, with the latter showing highly motile and invasive properties [
8,
9]. In general, this process is a fundamental event both in the early stage of embryonic development and in pathophysiological situations, including wound healing, chronic inflammation, and carcinoma progression [
7]. Several studies have reported that functional loss or down-regulation of E-cadherin is a hallmark of EMT [
10,
11], and transcriptional control of E-cadherin during EMT seems to be required. Although EMT entails the down-regulation of other epithelial-specific genes, such as those for components of tight and gap junctions or desmosomes, E-cadherin down-regulation is thought to be inherent to EMT [
12]. MicroRNAs (miRNAs) are an evolutionarily conserved family of small (a class of 22-nucleotide) noncoding RNAs, known to be potent modifiers of gene expression at a posttranscriptional level. They regulate multiple cellular processes such as tumorigenesis and metastasis by down-regulating gene expression in various malignancies, including HCC [
13]. microRNA-26a (miR-26a), a member of the miR-26 family, has been considered to be a potential tumor suppressor in HCC [
14,
15]. miR-26a has been reported to suppress tumor growth and metastasis of HCC through the interleukin (IL)-6-Stat3 signaling pathway [
16], and down-regulation of miR-26a in tumor tissue was associated with poor overall survival for patients who underwent curative surgery for HCC [
17]. In our previous study, we found that miR-26a indirectly suppresses tumor progress in HCC by inhibiting tumor angiogenesis and suppressing intratumoral macrophage infiltration [
14,
18]. However, how miR-26a modulates tumor progression in a direct manner remains poorly understood. It was reported that miR-26a mediated E-cadherin expression, the hallmark of EMT, in oral tongue squamous cell carcinoma, and the enhancer of zeste homolog 2 (EZH2) was the presumed key molecule that mediated miR-26a-induced down-regulation of E-cadherin expression [
19]. However, whether miR-26a plays a crucial role in EMT regulation and its underlying mechanism in HCC remains unknown. In the present study, we aimed to investigate the functional role of miR-26a in EMT and consider its potential as a therapeutic target in HCC.