In the current study, our results demonstrated that miR-589-5p expression was dramatically upregulated in HCC tissues using in situ hybridization, which was correlated with poor tumor differentiation degree, increased AFP levels, clinical stage, distant metastatic status and venous invasion in HCC patients. Importantly, HCC patients with high miR-589-5p score exhibited shorter overall survival and early recurrence-free survival compared with those with low miR-589-5p score. Therefore, our results indicate that miR-589-5p may be used as a potential clinical diagnostic biomarker to facilitate early detection and diagnosis of HCC.
In the vast majority of human cancer types, miR-589-5p was reported to be down-regulated and function as a tumor-suppressive miRNA, including endometrial carcinoma , prostate cancer , non-small cell lung cancer  and acute myeloid leukemia . However, in the HCC context, several lines of evidence have reported that miR-589-5p was remarkably upregulated in clinical HCC tissues, and overexpression of miR-589-5p significantly contributed to the progression and aggressiveness of HCC to varying mechanisms [11, 12]. These studies suggested that the oncogenic or tumor suppressive roles of miR-589-5p vary in different types of cancer. Importantly, high levels of miR-589-5p were positively associated with shorter overall survival in HCC patients [11, 12] and early recurrence-free survival . However, overexpression of miR-589-5p was mainly detected using quantitative real-time PCR (qRT-PCR) technique, and expression levels of miR-589-5p were influenced by multiple factors, including tissue storage duration, RNA extraction method, the specificity of PCR primers and so on, which to some extent influenced the clinical significance of miR-589-5p in diagnosis and prognosis of HCC. Thus, a more reliable and commonly used clinical technique, such as in situ hybridization, is required to further determine the clinical significance of miR-589-5p in HCC patients. In the current study, through in situ hybridization technique, we further examined expression score of miR-589-5p in 113 HCC tissues, and found that miR-589-5p score was dramatically upregulated in HCC tissues compared with that in non-malignant tissues. Further investigation showed that high score of miR-589-5p was observed in HCC patients with poor tumor differentiation, increased AFP levels, advanced clinical stage, distant metastatic status and venous invasion. Importantly, high miR-589-5p score predicted poor overall survival and early recurrence-free survival in HCC patients compared with those with low miR-589-5p score. Collectively, our results indicate that miR-589-5p may hold a promising applicable value to facilitate early diagnosis and predict prognosis in HCC patients from a clinical perspective.
More and more momentum has shed light on metastatic phenotype of cancer, which contributes to the vast majority of cancer-related deaths [18, 19]. For HCC, metastatic behavior is also commonly observed in this type of tumor characterized by the abundant blood flow, where aggressiveness of HCC is mediated by both intrahepatic metastases, as well as distant target organ metastasis to the lungs, bones, brain and adrenal gland [20, 21], which significantly contributes to poorer prognosis in HCC patients . Notably, our results in this study presented that overexpression of miR-589-5p was associated with poor prognosis in HCC patients. In addition, statistical analysis further showed that overexpression of miR-589-5p was positively correlated with venous invasion and M stage (distant metastasis). This finding supported the notion that miR-589-5p may be implicated in metastatic HCC, which further contributes to poor prognosis in HCC patients. However, the prognostic significance and functional role of miR-589-5p in metastatic HCC remain to be further elucidated in the following work in the future.
Paradoxically, Zhang and the colleagues have reported that miR-589-5p was reduced in CD90+ MHCC97H and MHCC97L compared with CD90− cells, which predicted poor overall and disease-free survival in HCC patients. Furthermore, Zhang et al found that miR-589-5p functioned as a tumor-suppressive miRNA to inihibit cancer stem cell-like traits and tumorigenesis of HCC cells . In our previous study, our results demonstrated that miR-589-5p was upregulated in HCC tissues and overexpression of miR-589-5p was associated with poor prognosis in HCC patients, which was further validated in Xu’s study , as well as several independent publicly available HCC datasets, including TCGA, E-GEOD-36918 and E-GEOD-31384 . Similarly, our finding of the current study further determined that miR-589-5p was overexpression in HCC tissues compared with that in adjacent tumor normal tissue using in situ hybridization. Mechanistically, the findings from our previous study showed that amplification was the primary mechanism responsible for miR-589-5p overexpression in HCC tissues , clarifying that miR-589-5p is mainly upregulated in HCC tissue. The discrepancy about the differential expression levels and different prognostic role of miR-589-5p expression in HCC patients in different studies may be explained by the different sample number analyzed: there were 136 HCC tissue samples used in our previous study  and TCGA dataset (n = 372); while only 40 HCC tissue samples were used in Zhang’s study. Therefore, our results in combination with Xu’s study indicate that overexpression of miR-589-5p is closely correlated with poor prognosis in HCC patients.