Clinical value and function of lncRNA MALAT1 in hepatocellular carcinoma: a comprehensive study with original detection, meta-analysis and in vitro verification

Background: Hepatocellular carcinoma (HCC) is known as a malignant neoplasm with a high metastasis rate, especially intrahepatic metastasis and poor prognosis. Recent studies have indicated that long noncoding RNAs (lncRNAs) may play an important role in HCC. As the first discovered lncRNA, the metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been explored in various cancers. However, the function of MALAT1 in HCC still remains unclear. The aim of this study was to investigate the clinical significance of MALAT1 in HCC with original detection and a meta-analysis, and further to verify the biological functions of MALAT1 in vitro. Methods: RT-qPCR was used to examine the expression of MALAT1 in 95 paired HCC cases. A meta-analysis of three available studies was also performed to evaluate the association between MALAT1 expression and clinical features in HCC. In addition, the biological functions on cell growth and apoptosis were investigated with four HCC cell lines (HepG2, SMMC-7221, Hep3B and SNU-449) via different in vitro assays. Results: Significantly upregulated MALAT1 was found in the current 95 HCC tissues compared with noncancerous adjacent hepatic tissues. The higher MALAT1 level was remarkably correlated with several clinicopathological parameters, such as tumor nodes (r=0.302, P=0.003), metastasis (r=0.358, P<0.001), TNM stage (r=0.340, P=0.001), and four established markers (nm23, MTDH, p53, VEGF). Meta-analysis further showed that the overexpressed MALAT1 was positively correlated with AFP level (OR=2.37, 95% CI: 1.19-4.73, P=0.002). Additionally, after MALAT1 was silenced in HCC cells, especially in HepG2 and SMMC-7221, the cell growth was suppressed and apoptosis was promoted notably. Conclusion: MALAT1 may play an essential role in the development and deterioration in HCC, in particular in cell growth and apoptosis. Following with the further research, understanding of MALAT1 may make great headway and MALAT1 gains the potential to act as a biomarker in diagnosis, prognosis prediction and targeted therapy in HCC.