LncRNA TP73-AS1 regulates miR-495 expression to promote migration and invasion of nasopharyngeal carcinoma cells through junctional adhesion molecule A.

The main obstacle to the treatment of nasopharyngeal carcinoma (NPC) is metastasis. Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are highly involved in the progression of NPC. In this study, we aimed to explore the regulatory role of lncRNA P73 antisense RNA 1 T (TP73-AS1) and miR-495 in migration and invasion of NPC cells. The expression levels of TP73-AS1, miR-495, and junctional adhesion molecule A (JAM-A) in NPC tissue samples and cell lines were examined by quantitative real-time PCR (qRT-PCR) and/or Western blot. NPC cells were transfected with vectors overexpressing TP73-AS1, short hairpin RNA (shRNA) against TP73-AS1, shRNA against JAM-A, miR-495 mimics, miR-495 inhibitor, and their corresponding negative controls as designated. The MTT assay, cell migration assay, and transwell assay were performed to detect cell viability, migration, and invasion, respectively. Dual-luciferase reporter assay was performed to confirm the binding of TP73-AS1 and miR-495, and miR-495 and JAM-A. TP73-AS1 and JAM-A were significantly upregulated while miR-495 was markedly downregulated in NPC tissues and cell lines compared to normal controls. The overexpression of TP73-AS1 promoted migration and invasion of NPC cell line CNE-2. TP73-AS1 targeted miR-495 and negatively regulated its expression. TP73-AS1 upregulated the expression of JAM-A through miR-495. TP73-AS1 mediated migration and invasion of CNE-2 cells via upregulating JAM-A. LncRNA TP73-AS1, miR-495, and JAM-A are involved in migration and invasion of NPC cells. The TP73-AS1/miR-495/JAM-A axis may serve as a therapeutic target for the treatment of NPC.

Effects and Mechanism of Action of Artemisinin on Mitochondria of Plasmodium berghei.

OBJECTIVE: To study the antimalarial effects and mechanisms of artemisinin (Qinghaosu in Chinese, QHS) on mitochondria in mice infected with Plasmodium berghei. METHODS: A total of 108 C57 mice infected with Plasmodium berghei were randomly divided into 3 groups by weight: the control group, 200 and 400 mg/kg QHS groups. The two QHS treatment groups were further divided into 4 sub-groups with 12 animals each time according to the treatment time, 0.5, 1, 2, and 4 h. Normal saline was intragastrically (i.g.) administered to the control group. The other two groups received different doses of QHS by i.g. administration. Animals were treated once with QHS for different detection time as follows: 0.5, 1, 2, and 4 h. The mitochondrial energy metabolism, oxidative damage, membrane potential, and membrane permeability and other indexes were detected. RESULTS: After administration of 200 and 400 mg/kg QHS, adenosine triphosphate (ATP) levels in Plasmodium and its mitochondria were reduced (P<0.05), the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) were increased (P<0.05), and the activity of superoxide dismutase (SOD) was also increased (P<0.05). At the same time, the membrane potential of the mitochondria was reduced and the degree to which the membrane permeability transition pore was opened was irreversibly increased (P<0.05). CONCLUSIONS: Mitochondria in Plasmodium were the targets of QHS, which can adversely affect mitochondrial energy metabolism, oxidative damage, membrane potential, and membrane opening, and ultimately exert an antimalarial effect.