Clinical significance of microRNA 138 and cyclin D3 in hepatocellular carcinoma

Background: MicroRNA 138 (miR-138) is recently shown to inhibit tumor growth and block cell cycle arrest of hepatocellular carcinoma (HCC) by targeting cyclin D3 (CCND3). The aim of this study was to investigate the clinical significance of miR-138 and CCND3 in human HCC, which remains unclear.

Methods: Quantitative real-time polymerase chain reaction analysis was performed to detect the expression levels of miR-138 and CCND3 messenger RNA (mRNA) in 180 self-pairs of HCC and noncancerous liver tissues.

Results: Compared with noncancerous liver tissues, the expression levels of miR-138 in HCC tissues were significantly downregulated (P < 0.001), whereas the expression levels of CCND3 mRNA in HCC tissues were significantly upregulated (P < 0.001). There was a negative correlation between miR-138 and CCND3 mRNA expression in HCC tissues (r = -0.56, P = 0.02). Additionally, statistical analysis showed that the combined miR 138 downregulation and CCND3 upregulation (miR-138-low-CCND3-high) was significantly associated with the advanced tumor-node-metastasis stage (P = 0.008) and the presence of portal vein invasion (P = 0.008) and lymph node metastasis (P = 0.01). More importantly, a significant trend was identified between the combined expression of miR-138-low-CCND3-high in HCC and worsening clinical prognosis. Multivariate survival analysis further recognized miR-138-low-CCND3-high expression as an independent prognostic factor for patients with HCC.

Conclusions: Our data suggest that the combined expression of miR-138 and its direct target CCND3 may be correlated with significant characteristics of HCC. MiR-138 downregulation and CCND3 upregulation maybe concurrently associated with prognosis in patients with HCC.