Circ_0081054 facilitates melanoma development via sponging miR-637 and regulating RAB9A.

BACKGROUND: Accumulating evidence announces that aberrantly expressed circRNAs were closely related to the development of human cancers. However, the role and mechanism of multiple circRNAs remain unclear. Our work aimed to disclose the functional role and mechanism of circ_0081054 in melanoma. METHODS: Quantitative real-time polymerase chain reaction assay was utilized to detect circ_0081054, microRNA-637 (miR-637) and RAB9A (member RAS oncogene family) mRNA expression. Cell proliferative ability was evaluated via Cell Counting Kit-8 and colony formation assay. Cell invasion was assessed by using wound healing assay. RESULTS: The significant upregulation of circ_0081054 was detected in melanoma tissues and cells. The proliferation, migration, glycolytic metabolism, and angiogenesis in melanoma cells were suppressed, while apoptosis was promoted following the silence of circ_0081054. In addition, circ_0081054 could target miR-637, and miR-637 inhibitor could reverse the effects of circ_0081054 deficiency. Furthermore, RAB9A was a target gene for miR-637 and RAB9A overexpression could reverse the effects of miR-637 overexpression. In addition, the deficiency of circ_0081054 hampered tumor growth in vivo. Moreover, circ_0081054 could regulate RAB9A expression by sponging miR-637. CONCLUSION: All results indicated that circ_0081054 promoted the malignant behaviors of melanoma cells partly by regulating the miR-637/RAB9A molecular axis.

CircRNA circ_0067772 aggravates the malignant progression of cutaneous squamous cell carcinoma by regulating miR-1238-3p/FOXG1 axis.

BACKGROUND: Cutaneous squamous cell carcinoma (CSCC) is a severe malignancy derived from skin. Dysregulated circular RNAs (circRNAs) might play vital roles in tumor development. OBJECTIVE: Here, we aimed to explore the function of a novel circRNA circ_0067772 in CSCC. METHODS: Quantitative real-time PCR (qRT-PCR) or Western blot assay was performed to determine the expression of circ_0067772, microRNA (miR)-1238-3p and forkhead box protein G1 (FOXG1). Cell proliferation was assessed by Cell Counting Kit-8 (CCK-8) assay and colony formation assay. Transwell assay and wound healing assay were employed to examine cell metastasis. Flow cytometry was employed to monitor cell cycle and apoptosis. The target association between miR-1238-3p and circ_0067772 or FOXG1 was validated by dual-luciferase reporter assay. Moreover, role of circ_0067772 in vivo was investigated via xenograft model in nude mice. RESULTS: Circ_0067772 and FOXG1 were upregulated, while miR-1238-3p was downregulated in CSCC tissues and cells. Circ_0067772 knockdown conferred inhibitory effects on cell proliferation, migration and invasion of CSCC cells. MiR-1238-3p served as a target of circ_0067772, whose silencing could reverse circ_0067772 knockdown-induced inhibitory impact on the malignant cellular behaviors. Circ_0067772 positively regulated FOXG1 expression by antagonizing miR-1238-3p. Additionally, miR-1238-3p could repress CSCC cell proliferation, migration and invasion by targeting FOXG1. Also, circ_0067772 knockdown hindered CSCC tumor growth in vivo. CONCLUSION: Our study identified a novel oncogenic circRNA and the involvement of circ_0067772/miR-1238-3p/FOXG1 axis in CSCC development, providing a target for CSCC therapy.

A Network Pharmacology Approach to Uncover the Molecular Mechanisms of Herbal Formula Kang-Bai-Ling for Treatment of Vitiligo.

BACKGROUND: Kang-bai-ling (KBL), a Chinese patent medicine, has been demonstrated as an effective therapy for vitiligo in China. However, the pharmacological mechanisms of KBL have not been completely elucidated. METHODS: In this study, the potential multicomponent, multitarget, and multipathway mechanism of KBL against vitiligo was clarified by using network pharmacology-based strategy. In brief, potential targets of KBL were collected based on TCMSP databases, followed by network establishment concerning the interactions of potential targets of KBL with well-known therapeutic targets of vitiligo by using protein-protein interaction (PPI) data. As a result, key nodes with higher level of seven topological parameters, including "degree centrality (DC)," "betweenness centrality (BC)," "closeness centrality (CC)," "eigenvector centrality (EC)," "network centrality (NC)," and "local average connectivity (LAC)" were identified as the main targets in the network, followed by subsequent incorporation into the ClueGO for GO and KEGG signaling pathway enrichment analysis. RESULTS: In accordance with the topological importance, a total of 23 potential targets of KBL on vitiligo were identified as main hubs. Additionally, enrichment analysis suggested that targets of KBL on vitiligo were mainly clustered into multiple biological processes (associated with DNA translation, lymphocyte differentiation and activation, steroid biosynthesis, autoimmune and systemic inflammatory reaction, neuron apoptosis, and vitamin deficiency) and related pathways (TNF, JAK-STAT, ILs, TLRs, prolactin, and NF-κB), indicating the underlying mechanisms of KBL on vitiligo. CONCLUSION: In this work, we successfully illuminated the "multicompounds, multitargets" therapeutic action of KBL on vitiligo by using network pharmacology. Moreover, our present outcomes might shed light on the further clinical application of KBL on vitiligo treatment.

[Glycyrrhizin inhibits IFN-γ-induced CXCL10 by suppressing the JAK/STAT1 signal pathway in HaCaT cells].

Objective To detect the effect of glycyrrhizin (GL) on the expression of CXCL10 induced by IFN-γ in HaCaT cells. Methods HaCaT cells were cultured in vitro. IFN-γ at the dosage of 10 ng/mL was used to establish the model group. GL (0.5 mmol/L), JAK1/2 inhibitor CYT387 (15 nmol/L), and combined therapy of GL and CYT387 were administrated in IFN-γ-treated HaCaT cells, respectively. Cell viability was detected by MTT assay. The expression of CXCL10 was assessed via real-time quantitative PCR and ELISA. Protein phosphorylation of the JAK1/2 and STAT1 was determined using western blot analysis. Results GL decreased IFN-γ-induced keratinocyte disruption. Moreover, GL had no significant effect on cell viability. Both GL and JAK1/2 inhibitor CYT387 down-regulated the expression of CXCL10 in HaCaT cells induced by IFN-γ. Its expression of CXCL10 mRNA was markedly lower in GL and CYT387 combined with GL group than that in CYT387 group. The phosphorylation of JAK1/2 and STAT1 declined by GL. Conclusion GL inhibits the activation of IFN-γ- mediated JAK/STAT1 signaling, thereby reducing CXCL10 level in HaCaT cells.