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Folate receptor alpha (FRα) is over-expressed in numerous epithelial malignancies, however, the association between FRα and cervical cancer remains unclear. The purpose of this study was to explore the effects of FRα on cervical cancer and its regulation of the ERK signaling pathway. In this case-control study, moderate/strong expression of FRα, phosphorylated ERK1/2 (p-ERK1/2), p-c-Fos, and p-c-Jun proteins was increased with the progressive severity of cervix lesions (P < 0.05). Moreover, the expression levels of p-ERK1/2, p-c-Fos, and p-c-Jun proteins was positively correlated with those of FRα protein in cervical squamous cell carcinoma (SCC) group (P < 0.05). In vitro experiment indicated down-regulation of FRα by siRNA suppressed cell proliferation, promoted cell apoptosis, induced cell cycle arrest at G0/G1 phase, and reduced expression of p-ERK1/2, p-c-Fos, and p-c-Jun proteins. The results suggest that FRα is associated with the progression of cervical cancer and regulates cervical cancer cells growth through phosphorylating ERK1/2, c-Fos, and c-Jun, which are key factors of the ERK signaling pathway. Therefore, FRα may be an effective target for early detection and therapy of cervical cancer. [ABSTRACT FROM AUTHOR]

Thrombocytopenia is a critical complication after radiation therapy and exposure. Dysfunction of megakaryocyte development and platelet production are key pathophysiological stages in ionizing radiation (IR)-induced thrombocytopenia. Protein kinase C (PKC) plays an important role in regulating megakaryocyte development and platelet production. However, it remains unclear how PKC regulates IR-induced megakaryocyte apoptosis. In this study, we found that pretreatment of PKC pan-inhibitor Go6983 delayed IR-induced megakaryocyte apoptosis, and inhibited IR-induced mitochondrial membrane potential and ROS production in CMK cells. Moreover, suppressing PKC activation inhibited cleaved caspase3 expression and reduced p38 phosphorylation levels, and IR-induced PKC activation might be regulated by p53. In vivo experiments confirmed that Go6983 promoted platelet count recovery after 21 days of 3 Gy total body irradiation. Furthermore, Go6983 reduced megakaryocyte apoptosis, increased the number of megakaryocyte and polyploid formation in bone marrow, and improved the survival rate of 6 Gy total body irradiation. In conclusion, our results provided a potential therapeutic target for IR-induced thrombocytopenia. [ABSTRACT FROM AUTHOR]

Bone cancer pain (BCP) causes troubles and burdens to patients globally. Increasing evidence proved that neuromedin U receptor 2 (NMUR2) was involved in pains. Our study was performed to investigate the role of NMUR2 on BCP and the underlying mechanism. The rats were raised and BCP rat model was established by injection with Walker 256 cells. The RNA and protein expression levels of NMUR2 in rat neurons-dorsal spinal cord cells, RNdsc cells were detected by qRT-PCR and western blot. The administration with NMUR2 was via intrathecal injection with siRNA to silence NMUR2. The tolerance of rat to pain was measured by mechanical allodynia test and presented by paw withdrawal threshold (PWT) value. The effects on protein kinase C (PKC)/extracellular regulated protein kinases (ERK) and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) signal pathways were examined by western blot. The expression of NMUR2 in both mRNA and protein levels was upregulated in BCP rat model. In addition, siRNA injection significantly decreased the expression of NMUR2 on the 3rd, 7th and 14th day. BCP group revealed lower PWT value compared with control while NMUR2 silence increased the PWT value compared with negative control. The phosphorylation of PKC, ERK, PI3K and AKT was increased in BCP model while was decreased by si-NMUR2. PKC/ERK and PI3K/AKT inhibitor administration increased the PWT value compared with BCP group. si-NMUR2 alleviates BCP via inactivation of PKC/ERK and PI3K/AKT signal pathways. • NMUR2 is upregulated in BCP rat model. • si-NMUR2 alleviates nociception in BCP rat model. • si-NMUR2 relieves nociception by inactivating PKC/ERK and PI3K/AKT pathways. [ABSTRACT FROM AUTHOR]