miR-7-5p Promotes Hepatic Stellate Cell Activation by Targeting Fibroblast Growth Factor Receptor 4

Abstract

Aims. Fibroblast growth factor receptor 4 (FGFR4) is a key mediator that protects the liver from chronic injury. MicroRNA-7 (miR-7) is a tumor suppressor and associated with lipid homeostasis in the liver. This study was designed to examine the role of the miR-7-5p/FGFR4 axis in liver fibrogenesis. Methods. TargetScan was employed to predict microRNAs that targeted FGFR4 on the 3′-untranslated region (3′-UTR). miR-7-5p and FGFR4 expression in pathological liver tissues and LX-2 cells was determined using qRT-PCR and an immunoblotting assay. A dual-luciferase assay was conducted to validate the target prediction. A Cell Counting Lit-8 assay was performed to assess the proliferation ability of LX-2 cells. Hydroxyproline content in LX-2 cells was measured using a hydroxyproline assay. The expression of hepatic stellate cell (HSC) activation markers was examined using qRT-PCR and an immunoblotting assay. Results. FGFR4 was a putative target of miR-7-5p. In LX-2 cells, miR-7-5p targeted FGFR4 by binding to 3′-UTR. FGFR4 was downregulated, but miR-7-5p was markedly enhanced in the liver samples as the degree of liver fibrosis rose. miR-7-5p was negatively associated with FGFR4 expression in liver tissues. The miR-7-5p inhibitor blocked the lipopolysaccharide-induced proliferation and activation of LX-2 cells, and FGFR4 overexpression inhibited LX-2 cell proliferation and activation triggered by miR-7-5p. Conclusion. miR-7-5p promotes HSC proliferation and activation by downregulating FGFR4.

TUMOR MICROENVIRONMENT-ASSOCIATED miR-7-5p, miR-19a-3p, AND miR-23b-3p EXPRESSION IN PROSTATE CANCER WITH DIFFERENT PROGRESSION RISK

“…We found that the level of miR-7-5p expression also correlates with the degree of in-filtration of the PCa tissue by tumor-associated macrophages. These facts are consistent with the literature data [32,33] and allow us to assert the participation of these miRNAs in the formation T. Borikun, O. Mushii, A. Pavlova, T. Burda, T. Zadvornyi of the TME of PCa. Along with this, the study [34] has demonstrated that miR-7-5p participates in the processes of hyaluronan-dependent differentiation of fibroblasts by inhibiting EGFR signaling.…”

MiR-7-5p attenuates vascular smooth muscle cell migration and intimal hyperplasia after vascular injury by NF-kB signaling

“…miR-7-5p is involved in multiple disease models by regulating the targeted genes. It has been reported that miR-7-5p enhances activation of hepatic stellate cell by regulating fibroblast growth factor receptor 4 [ 27 ]. miR-7-5p modulates brain edema after intracerebral hemorrhage [ 28 ].…”

Integrative Analysis of the lncRNA-Associated ceRNA Regulatory Network Response to Hypoxia in Alveolar Type II Epithelial Cells of Tibetan Pigs

“…Many genes specifically increase related transcriptional activities and regulate a series of metabolic activities in the body during longterm adaptation to hypoxic environments. MiR-7-5p is a fascinating miRNA that plays diverse roles in tumor suppression; it inhibits the invasion abilities of tumor cells by directly targeting PI3K/Akt, FAK, and KLF4 expression and may be a useful therapeutic target for the diagnosis and treatment of patients with glioblastoma (65)(66)(67). miR-20b inhibits the expressions of autophagy-related proteins that are induced by hypoxia/reoxygenation injury via ULK1 (68).…”