{Reference Type}: Journal Article
{Title}: Long non-coding RNA HULC regulates TLR4 expression by acting as ceRNA to attract miR-663b in skin fibroblasts of pediatric burns.
{Author}: Liu Y;Qi X;Zhou Y;
{Journal}: Am J Transl Res
{Volume}: 13
{Issue}: 4
{Year}: 2021
{Factor}: 3.94
{Abstract}: <B>OBJECTIVE: </B>The study aims to elucidate the impact of LncRNA HULC in human skin fibroblasts (HSF) after burns in children. HULC might act as endogenous sponges for miR-663b to regulate the gene expression of TLR4.<BR><B>METHODS: </B>This study included 46 children with deep second-degree burns. On the 5th day after the injury, eligible samples from all patients were collected. HSF cells were selected to establish a thermal-injured model. qRT-PCR was applied to detect the expression of HULC, miR-663b, and TLR4 mRNA in burn wound and normal skin tissue. The dual-luciferase reporter and RIP assay were performed to explore a targeted binding relationship between HULC and miR-663b, or miR-663b and TLR4. Cell proliferation and invasion were evaluated through the assay of CCK-8 and transwell assay. The expression levels of α-SMA, Collagen I, MMP-1, and TIMP-1, which are associated with extracellular matrix (ECM) production, were examinated by western blot.<BR><B>RESULTS: </B>HULC and TLR4 mRNA expression were reduced on the 5th day after thermal injury in burn wounds, while miR-663b expression increased significantly (P<0.05), when compared to expression in the normal tissue. HULC and TLR4 mRNA concentration in HSF cells showed a transient increase after thermal injury, and a gradual decline with time was observed subsequently when compared to the control group. An inverse expression of miR-663b with the expression of HULC and TLR4 mRNA was observed simultaneously (P<0.05). A deficiency of HULC promotes the proliferation, invasion, and ECM synthesis of HSF cells with thermal injury; HULC functions as a ceRNA of miR-663b. Inhibitors of miR-663b partially rescued the effects on thermal-injured HSF cells induced by HULC deficiency (P<0.05). TLR4 is a target gene of miR-663b. The up-regulation of TLR4 also partially reversed the effect on the thermal-injury of HSF cells resulting from HULC deficiency (P<0.05).<BR><B>CONCLUSIONS: </B>LncRNA HULC may function as a molecular sponge to regulate the expression of the miR-663b/TLR4, and thereby inhibit the proliferation, invasion, and ECM synthesis of thermal-injured HSF cells. HULC knockdown might significantly promote wound healing in children after burns.