Effect of artificial skin membrane on the expression of miR-155 and miR-506-3p in patients with second-degree burns.

OBJECTIVE: To investigate the effect of artificial skin on the expression of miR-155 and miR-506-3p in patients with second-degree burns. METHODS: The study subjects included 50 patients with second-degree burns treated from July 2019 to July 2021. The control group received routine nursing, while the research group received both routine and artificial skin intervention simultaneously. The changes in wound tissue fibrosis and prognosis were observed. The expression levels of miR-155 and miR-506-3p and their downstream regulatory factors were detected and correlated with the rehabilitation of patients after artificial skin treatment. RESULTS: After treating second-degree burns with artificial skin membranes, the patient's wound tissue fibrosis and inflammation level improved. At the same time, the expression levels of miR-155 and miR-506-3p in related tests were higher than those in patients with available treatment. CONCLUSION: The effect of artificial skin membrane on the wound healing of second-degree burn patients may be realized by influencing the expression levels of miR-155 and miR-506-3p and their related signaling pathways.

MicroRNA-506-3p initiates mesenchymal-to-epithelial transition and suppresses autophagy in osteosarcoma cells by directly targeting SPHK1.

Osteosarcoma (OS) is the most common malignant bone tumor. In cancer cells, autophagy is related to epithelial-to-mesenchymal transition (EMT). Although microRNA (miR)-506-3p has been demonstrated to act as a tumor suppressor in OS, its role in regulating the EMT process and autophagy remains unknown. The results showed that miR-506-3p directly inhibited the expression of sphingosine kinase 1 (SPHK1) in 143B and SaOS-2 cells. The invasive capability of OS cells was reduced following miR-506-3p mimics transfection, and restored when SPHK1 was overexpressed simultaneously. Further, miR-506-3p mimics initiated mesenchymal-to-epithelial transition (MET) - E-cadherin expression was upregulated, whilst vimentin and fibronectin were downregulated. The basal autophagy flux (LC3II/I) was suppressed by miR-506-3p mimics. The alterations induced by miR-506-3p mimics were partly reversed by SPHK1 overexpression or treatment of rapamycin. Meanwhile, treatment of SPHK1-transfected cells with 3-methyladenine inhibited EMT. The data suggest that miR-506-3p initiates MET and suppresses autophagy in OS cells by targeting SPHK1.

Down-regulation of long noncoding RNA HOXA11-AS nullifies the impact of microRNA-506-3p on chondrocytes proliferation and apoptosis in osteoarthritis.

OBJECTIVES: This study was directed towards exploring the impacts of lncRNA HOXA11-AS-mediated microRNA (miR)-506-3p on chondrocytes proliferation and apoptosis in osteoarthritis (OA). METHODS: The articular cartilages were provided by OA patients who received total knee arthroplasty, and Human Chondrocyte (HC)-OA (HCOA) was also attained. The miR-506-3p and HOXA11-AS expressions in articular cartilages from OA patients and HCOA cells were analyzed via qPCR. After gain- and loss-of-function assays in HCOA cells, MTT assay and flow cytometry (FC) were used for assessing cell viability and apoptosis, accordingly. The levels of PIK3CA, AKT, and mTOR as well as AKT and mTOR phosphorylation levels assessed using western blotting (WB). The targeting correlation of HOXA11-AS and miR-506-3p as well as miR-506-3p and PIK3CA was assessed through Dual-Luciferase Reporter gene Assay (DLRA). RESULT: The articular cartilages from OA patients and Human Chondrocyte (HC)-OA (HCOA) cells showed increased HOXA11-AS and decreased miR-506-3p. Mechanistically, HOXA11-AS was capable of binding to miR-506-3p to increase PIK3CA, the target gene of miR-506-3p. miR-506-3p suppression facilitated HCOA cell proliferation and reduced their apoptosis, which was nullified by further silencing HOXA11-AS or silencing PIK3CA. The down-regulation of HOXA11-AS disrupted the PI3K/AKT/mTOR pathway, which was counteracted by further miR-506-3p inhibition. CONCLUSION: The silencing of HOXA11-AS might block the PI3K/AKT/mTOR pathway through miR-506-3p up-regulation, thereby restricting HCOA cell proliferation and provoking apoptosis.

YY1 accelerates oral squamous cell carcinoma progression through long non-coding RNA Kcnq1ot1/microRNA-506-3p/SYPL1 axis.

OBJECTIVE: Ying Yang1 (YY1) has already been discussed in oral squamous cell carcinoma (OSCC), but the knowledge about its mediation on long non-coding RNA KCNQ1 overlapping transcript 1/microRNA-506-3p/synaptophysin like 1 (Kcnq1ot/miR-506-3p/SYPL1) axis in OSCC is still in its infancy. Hence, this article aims to explain the mechanism of YY1/Kcnq1ot1/miR-506-3p/SYPL1 axis in OSCC development. METHODS: YY1, Kcnq1ot1, miR-506-3p and SYPL1 expression levels were determined in OSCC tissues. The potential relation among YY1, Kcnq1ot1, miR-506-3p and SYPL1 was explored. Cell progression was observed to figure out the actions of depleted YY1, Kcnq1ot1 and SYPL1 and restored miR-506-3p in OSCC. OSCC tumorigenic ability in mice was examined. RESULTS: Elevated YY1, Kcnq1ot1 and SYPL1 and reduced miR-506-3p were manifested in OSCC. YY1 promoted Kcnq1ot1 transcription and up-regulated Kcnq1ot1 expression, thereby promoting OSCC cell procession. Silencing Kcnq1ot1 or elevating miR-506-3p delayed OSCC cell progression and silencing Kcnq1ot1 impeded tumorigenic ability of OSCC cells in mice. YY1-mediated Kcnq1ot1 sponged miR-506-3p to target SYPL1. CONCLUSION: YY1 promotes OSCC cell progression via up-regulating Kcnq1ot1 to sponge miR-506-3p to elevate SYPL1, guiding a novel way to treat OSCC.

MicroRNA-506-3p targets SIRT1 and suppresses AMPK pathway activation to promote hepatic steatosis.

Nonalcoholic fatty liver disease (NAFLD) is a complex type of liver disease that represents an important global health threat. The mechanistic basis of this disease remains incompletely understood. The present study sought to explore whether microRNA (miR)-506-3p served a functional role in the onset and/or progression of NAFLD. To that end, high levels of glucose were used to treat liver cancer cell lines (HepG2 and Huh7) to model hepatic steatosis, and the expression levels of miR-506-3p and its downstream target genes were assessed. The cells of this hepatic steatosis model were transfected with miR-506-3p mimic molecules to explore the effect of miR-506-3p overexpression on cell viability, target gene expression and AMP-activated protein kinase (AMPK) phosphorylation. Via bioinformatics approaches, sirtuin 1 (SIRT1) was identified as a potential miR-506-3p target gene with relevance in NAFLD, and this interaction was confirmed via luciferase reporter assay. In the hepatic steatosis model of the present study, miR-506-3p expression level was significantly increased, whereas SIRT1 mRNA/protein levels and AMPK phosphorylation levels were markedly decreased. Transfection of the cells with miR-506-3p mimics led to significant SIRT1 downregulation, while miR-506-3p inhibitor molecules exhibited the opposite effect, with similar trends observed in the phosphorylation status of AMPK. These results suggested that miR-506-3p can inhibit SIRT1 expression and associated AMPK phosphorylation in HepG2 and Huh7 cells in an in vitro hepatic steatosis model system. These data indicated that the miR-506-3p/SIRT1/AMPK axis may be valuable as a therapeutic target in patients affected by NAFLD.

Long noncoding RNA LINC01410 promotes the tumorigenesis of neuroblastoma cells by sponging microRNA-506-3p and modulating WEE1.

OBJECTIVE: Neuroblastoma (NBL) is an extra-cranial solid tumor in children. This study was attempted to investigate the regulatory mechanism of long noncoding RNA LINC01410 (LINC01410) on NBL. METHODS: The expression of LINC01410, miR-506-3p, and WEE1 in NBL was evaluated by quantitative real time polymerase chain reaction. The proliferation and colony formation ability of NBL cells were analyzed by MTT and colony formation assay. Flow cytometry assay was executed to measure the apoptosis and cell cycle. Dual-luciferase reporter assay was used to detect the targeted relationships among LINC01410, miR-506-3p, and WEE1. Additionally, the role of LINC01410 on NBL in vivo was evaluated according to a tumor xenograft model. RESULTS: The expression of LINC01410 and WEE1 was enhanced and miR-506-3p was inhibited in NBL. LINC01410 knockdown attenuated the cell proliferation, colony formation ability, and inhibited tumor growth. Moreover, LINC01410 silencing facilitated the apoptosis and arrested the cell cycle. LINC01410 interacted with miR-506-3p to elevate the WEE1 expression in NBL. Additionally, miR-506-3p inhibition or WEE1 overexpression weakened the reduction effects of sh-LINC01410 on cell proliferation, colony formation ability, apoptosis, and cell cycle. CONCLUSIONS: Knockdown of LINC01410 inhibited the development of NBL by miR-506-3p/WEE1 axis in vitro, which could serve as a potential therapeutic target for NBL therapy.

MicroRNA­506­3p reverses gefitinib resistance in non­small cell lung cancer by targeting Yes­associated protein 1.

Epidermal growth factor receptor­tyrosine kinase inhibitors, such as gefitinib, have been found to be clinically effective in the treatment of patients with non­small cell lung cancer (NSCLC). However, the therapeutic effect of gefitinib is often limited by the development of gefitinib resistance. MicroRNAs (miRNAs), a group of small non­coding RNAs, have been demonstrated to be frequently dysregulated in human malignancies. For instance, the downregulation of miR­506­3p has been reported in NSCLC patients. The aim of the present study was to determine the role and underlying molecular mechanism of miR­506­3p in the regulation of gefitinib sensitivity in NSCLC. A gefitinib­resistant PC­9 (PC­9GR) cell line was established, and reduced miR­506­3p expression was observed in PC­9GR cells as compared with that in parental cells. The results of cell cytotoxicity and cell apoptosis assays indicated that PC­9GR cells were more sensitive to gefitinib following the transfection with an miR­506­3p mimic, while transfection with an miR­506­3p antagonist reduced the sensitivity of PC­9GR cells to gefitinib. It was further revealed that Yes­associated protein 1 (YAP1) was directly suppressed by miR­506­3p in PC­9GR cells. The elevated sensitivity of PC­9GR cells to gefitinib following transfection with the miR­506­3p mimic was counteracted by the overexpression of YAP1. Furthermore, an inverse correlation between the miR­506­3p and YAP1 mRNA levels was detected in lung adenocarcinoma specimens. Collectively, the results of the present study suggested that the downregulation of miR­506­3p contributes to gefitinib resistance, and thus, the restoration of miR­506­3p may be a potential therapeutic approach for overcoming NSCLC gefitinib resistance.

Overexpression of microRNA-506-3p aggravates the injury of vascular endothelial cells in patients with hypertension by downregulating Beclin1 expression.

The aim of the present study was to measure the expression of microRNA (miRNA)-506-3p in the peripheral blood of patients with hypertension and to determine the biological functions and mechanisms of action of miR-506-3p. A total of 61 patients with primary hypertension were included in the present study. Peripheral blood was collected from all patients, as well as 31 healthy subjects who were included in a control group. The expression of miR-506-3p in peripheral blood was determined by reverse transcription-quantitative polymerase chain reaction. Human umbilical vein endothelial cells (HUVECs) were transfected with miR-506-3p mimics or miR-506-3p inhibitor. The proliferation and migration of HUVECs were determined using cell-counting kit 8 and Transwell assays, respectively. The cell cycle and apoptosis of HUVECs were detected by flow cytometry. The expression of Beclin1 (BECN1) protein, a potential target of miR-506-3p, was measured using western blotting. A dual-luciferase reporter assay was performed to determine the interaction between BECN1 and miR-506-3p. It was demonstrated that miR-506-3p expression in the peripheral blood of patients with patients was upregulated and dependent on the severity of hypertension. miR-506-3p overexpression inhibited the proliferation and migration of HUVECs. In addition, miR-506-3p inhibited the transition from the G1 phase to the S-phase in HUVECs. Overexpression of miR-506-3p promoted the apoptosis of HUVECs. Notably, miR-506-3p downregulated the expression of BECN1 by directly binding to its 3'-untranslated region. The present study demonstrated that miR-506-3p expression is elevated in the peripheral blood of patients with hypertension and is associated with the severity of hypertension. By downregulating BECN1 expression, miR-506-3p aggravates injury in vascular endothelial cells by inhibiting the proliferation and migration of HUVECs, as well as promoting their apoptosis.

MicroRNA-506-3p regulates neural stem cell proliferation and differentiation through targeting TCF3.

Neural stem cells (NSCs) are self-renewing, multipotent and undifferentiated precursors that retain the capacity for differentiation into both glial and neuronal lineages. MicroRNAs (miRNAs) are small noncoding RNAs that play important roles in cell development, differentiation and apoptosis. Recent studies have shown that TCF3 affects neural stem cell proliferation and differentiation. In this study, we predicted that microRNA-506-3p would target TCF3 and demonstrated that miR-506-3p negatively regulates TCF3 expression. The expression level of miR-506-3p was significantly increased during NSC differentiation. In addition, we found that miR-506-3p overexpression increased NSC differentiation and reduced NSC proliferation, indicating an important role of miR-506-3p in NSC. Moreover, the downstream of TCF3, Wnt signaling was significantly decreased with miR-506-3p transfection. These findings suggest that miR-506-3p played an important role in regulating NSC proliferation and differentiation via targeting TCF3, and provide a promising avenue for future in-depth research into the functions of miR-506-3p and TCF3 in nervous system development.