Knockdown of long noncoding RNA HUMT inhibits the proliferation and metastasis by regulating miR-455-5p/LRP4 axis in hepatocellular carcinoma

Abstract

The present study aimed at investigating the effects and mechanism of long noncoding RNA highly upregulated in metastatic triple-negative breast cancer lymph node (lncRNA HUMT) in hepatocellular carcinoma (HCC). Quantitative real-time polymerase chain reaction was used to assess the expression of HUMT, microRNA (miR)-455-5p, and low-density lipoprotein receptor-related protein 4 (LRP4) in HCC tissues. Colony forming and 5-ethynyl-2′-deoxyuridine assays were performed to assess cell proliferation. Transwell assay was performed to measure cell migration and invasion. Cell cycle distribution was assessed using flow cytometry. The protein expression of LRP4, proliferating cell nuclear antigen (PCNA), matrix metallopeptidase 2 (MMP-2), and MMP-9 was detected using western blot. Luciferase reporter assay and RNA immunoprecipitation assay was used to confirm the target association between miR-455-5p and HUMT or LRP4. In our study, the level of HUMT was enhanced in HCC tissues and cells. Cell proliferation, invasion, and migration in HCC cells were repressed by knockdown of HUMT, and knockdown of HUMT arrested cells in G1 phase and decreased the levels of PCNA, MMP-2, and MMP-9. MiR-455-5p was a target of HUMT. Lowexpression of miR-455-5p reversed the inhibitive influence on HCC cells induced by of HUMT silencing. LRP4 was a target of miR-455-5p and was negatively regulated by miR-455-5p. In addition, LRP4 expression was positively modified by HUMT, and LRP4 inhibited the inhibitory effects on HCC cells induced by HUMT silencing. In conclusion, HCC cell proliferation, invasion, and migration were restrained by knockdown of HUMT, which was related to the miR-455-5p/LRP4 axis.

Associations of genetically determined circulating proteins with breast cancer risk or survival

“…Many proteins are associated with BC survival in our study. Previous studies have indicated that high expression of LRP4 can inhibit the proliferation, invasion, and migration of hepatocellular carcinoma cells by affecting the miR-455-5p/LRP4 axis (Zou et al 2022). LRP4 is positively associated with BC survival, which suggests the protective role of LRP4.…”