High expression of microRNA-130b correlates with poor prognosis of patients with hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the third most common cause of mortality from cancer worldwide [1]. In China, HCC is the second highest cancer killer since the 1990s, which alone accounts for 53% of all liver cancer deaths worldwide [2]. More than 90% of HCC cases develop in chronically inflamed liver as a result of viral hepatitis, alcohol abuse and in increasing incidence in patients with non-alcoholic fatty liver disease [3]. Although the clinical staging systems for HCC have been used in routine clinical decision making, there is still a need to refine and complement outcome predictions. Modifications of these staging systems by the addition of new biomarkers are likely to improve the prognostic assessment of HCC patients and could therefore fulfill a clinical need [4]-[9].

MicroRNAs (miRNAs) are endogenously expressed, small interfering RNAs [10]. They are transcribed as precursor molecules that are subsequently processed into the active ~21 nucleotide mature miRNAs. The mature miRNA binds to the 3’untranslated region of the target mRNA through imperfect base pairing, producing translational arrest and/or degradation of the mRNA. A growing number of both direct and indirect evidence suggests a relationship between differential miRNA expression and cancer [11],[12]. miR-130b has been found to be deregulated in some types of cancers, including being overexpressed in gastric cancer [13],[14], glioma [15], and renal cell carcinoma(RCC) [16], while being downregulated in endometrial cancer [17] and papillary thyroid carcinoma [18]. Previously, Liu et al. reported that the expression level of miR-130b was upregulated in HCC tissues. Furthermore, circulating miR-130b in serum was a biomarker with clinical value for HCC screening [19]. However, whether miR-130b can serve as a prognostic biomarker of HCC has not been investigated. Therefore, in the present study, we investigated the feasibility of miR-130b as a novel prognostic biomarker for HCC.

A growing number of novel treatment strategies have been developed for HCC, including molecular targeted therapy, gene therapy, and immunotherapy. However, satisfactory therapeutic outcomes have not been achieved, and the survival rate of HCC is still low. A complete understanding of the molecular mechanisms underlying tumor initiation and progression is essential for novel prognostic and therapeutic approaches aimed at improving the outcome of patients with HCC. Over the last years, miRNAs are emerging as a new class of gene regulators involved in different malignancies.

The miR-130 family is formed by mature miR-130a and miR-130b that share the same seed sequence and are coded by two independent loci (miRBase Database). miR-130 has been found to linked to mesenchymal differentiation, immune cell function, and hypoxic response modulation [20]. miR-130 has also been validated as a peroxisome proliferator–activated receptor γ (PPARγ) regulator because it suppresses the adipogenic process through the binding to two distinct highly conserved sites located in the coding sequence and 3’UTR of the corresponding mRNA [20],[21]. miR-130b has been found to be deregulated in some types of cancers, including being overexpressed in gastric cancer [13],[14], glioma [15], and RCC [16], while being downregulated in endometrial cancer [17] and papillary thyroid carcinoma [18]. For example, Zhao et al. demonstrated that the deregulated expression of miR-130b was associated with poor prognosis and aggressive phenotype of pancreatic cancer, and miR-130b played an important role in the regulation of pancreatic cancer malignant behavior including cell proliferation and invasion by directly targeting STAT3, indicating that miR-130b might be applied as a potential prognostic biomarker and inhibitor in pancreatic cancer [22]. Previously, Liu et al. reported that the expression level of miR-130b was upregulated in HCC tissues. Furthermore, circulating miR-130b in serum was a biomarker with clinical value for HCC screening [19]. However, whether miR-130b can serve as a prognostic biomarker of HCC has not been investigated. Therefore, we investigated the feasibility of miR-130b as a novel prognostic biomarker for HCC.

In the present study, our results showed that miR-130b expression was significantly higher in HCC tissues compared with normal adjacent liver tissues. The relationships of the miR-130b with various clinical features of HCC were analyzed. The results revealed that a high level of miR-130b expression was correlated with serum AFP level, HBsAg status, tumor size, high histologic grade, and high TNM stage, suggesting that miR-130b might be involved in the carcinogenesis and metastasis of HCC. Furthermore, the 5-year OS of high miR-130b expression group was significantly shorter than that of low miR-130b expression group. Moreover, the 5-year DFS of high miR-130b expression group was also significantly shorter than that of low miR-130b expression group. In a multivariate Cox model, we found that miR-130b expression was an independent poor prognostic factor for both 5-year OS and 5-year DFS, indicating that high miR-130b level might be a promising non-invasive biomarker for prognosis of patients with HCC.

In conclusion, we demonstrated that miR-130b was significantly upregulated in HCC and correlated with poorer patients’ prognosis and it might be useful as a prognostic biomarker for HCC.