LINC00240 sponges miR-4465 to promote proliferation, migration, and invasion of hepatocellular carcinoma cells via HGF/c-MET signaling pathway

W.-J. Bu, Z. Fang, W.-L. Li, X. Wang, M.-J. Dong, Q.-Y. Tao, L. Zhang, Y.-Q. Xu

Department of Oncology, The Second Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China. xuyouqi@nucm.com.cn

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• Oncology

OBJECTIVE: LINC00240, as a novel long non-coding RNAs (lncRNAs), has never been studied in hepatocellular carcinoma (HCC). This research reported the expression and function of LINC00240 in HCC.

PATIENTS AND METHODS: LINC00240 expression in 180 HCC patients was downloaded from the Cancer Genome Atlas (TCGA) database. HCC patients’ survival was analyzed via Kaplan‑Meier analysis. The expression of LINC00240, miR-4465 and HGF in Hep3B and Huh7 cells were regulated by transfection. Cell viability was determined by MTT assay. Transwell experiment was used for the detection of cells migration and invasion abilities. The interaction between LINC00240, miR-4465 and HGF was reflected by Luciferase reporter assay. LINC00240, miR-4465, HGF and p-c-MET expression in HCC cells were researched by real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot.

RESULTS: TCGA data showed that high LINC00240 expression was markedly associated with lower survival of HCC patients (p = 0.036). LINC00240 expression was aberrantly upregulated in HCC cells. Silencing of LINC00240 significantly reduced HCC cells viability, migration and invasion. miR-4465 was a target gene of LINC00240. Silencing of LINC00240 reduced HCC cells viability, migration and invasion via directly promoting miR-4465 expression. HGF was target gene of miR-4465. miR-4465 up-regulation obviously suppressed HGF and p-c-MET expression. According to rescue experiment, LINC00240 silencing inhibited HCC cells viability, migration and invasion by suppressing HGF/c-MET signaling pathway via targeting miR-4465.

CONCLUSIONS: LINC00240 sponges miR-4465 to promote HCC cells proliferation, migration and invasion via HGF/c-MET signaling pathway.

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