lncRNA MALAT1 promotes HCC metastasis through the peripheral vascular infiltration via miRNA-613: a primary study using contrast ultrasound

Background: This study aimed to explore the specific pathogenesis of lncRNA MALAT1 promoting the invasion and metastasis of hepatocellular carcinoma (HCC) through peripheral blood vessels by regulating the expression of miRNA-613 molecule.

Methods: The data of 60 HCC metastatic patients and 60 HCC non-metastatic patients detected by the contrast-enhanced ultrasound (CEUS) in the Second Affiliated Hospital of Qiqihar Medical College from January 2020 to June 2021 were collected, as well as postoperatively retained HCC tissues and paired paracancer tissues (5 cm laterally from the edge of the cancer area), to study the changes of microangiogenesis in HCC tissues with CEUS. The correlation between CEUS grading and lncRNA MALAT1 in patients with HCC was analyzed through Pearson correlation analysis, lncRNA MALAT1 and miRNA-613 in HCC tissues of patients with HCC were detected by qRT-PCR, followed by the bioinformatic analysis for the relationship between lncRNA MALAT1 and miRNA-613. The Log-growing human HCC cell strain, HepG2, was selected for experiments. Adenovirus transfection knocked down lncRNA MALAT1 in HCC cells, which was divided into two groups (inhibitor-NC group and lncR-inhibitor group), followed by knocking down miRNA-613 on the basis of knocking down lncRNA MALAT1, which was divided into three groups (inhibitor-NC group, lncR-inhibitor groups, and lncR/miR613-inhibitor group). The expression of miRNA-613 and lncRNA MALAT1 in each group was detected by qRT-PCR. The migration and invasiveness of cells in each group were detected by Transwell assay.

Results: CEUS of HCC and Pearson correlation analysis showed that CEUS grading and lncRNA MALAT1 were positively correlated in patients with HCC. In HCC tissues of patients with HCC, lncRNA MALAT1 expressed high and miRNA-613 expressed low. The results of bioinformatic analysis showed the targeting of lncRNA MALAT1 and miRNA-613. Knocking down lncRNA MALAT1 could increase miRNA-613 expression significantly, and reduce the migration of HCC cells. Inhibiting miRNA-613 based on knocking down lncRNA MALAT1 could increase the survival and migration of HCC cells.

Conclusions: lncRNA MALAT1 can promote HCC metastasis through the peripheral vascular infiltration by inhibiting the level of MiRNA-613, which can, therefore, be used as a potential target for the treatment of HCC.