Cervical cancer (CC) is a prevalent malignancy in women, with the feature of metastasis and easy recurrence is responsible for a large proportion of global cancer deaths. Radiotherapy is one of the common treatment tools for CC patients with unresectable tumors. However, radio-resistance in patients could be a major reason for recurrence. Therefore, it is of significance to tunnel the molecular mechanism of radio-resistance in CC. MicroRNAs (miRNAs) are increasingly reported in the regulation of cancer progression and cellular response to radiotherapy and chemotherapy. miR-4429 is a newly discovered miRNA acting as a tumor-suppressor gene in multiple cancers, but its function in CC has never been explored yet. The current study tried to explore the role of miR-4429 in cell radio-sensitivity in CC.First, we validated the downregulation of miR-4429 in CC cells. Importantly, the association of miR-4429 with radio-resistance was validated by identifying the downregulation of miR-4429 in radio-resistant CC cells. Gain-and loss-of-function assays validated that miR-4429 sensitized CC cells to irradiation. Through bioinformatics tools, RAD51 recombinase (RAD51) was identified to be a target for miR-4429. RAD51 is known to be a crucial regulator for DNA damage repair and has been reported to influence cell radio-resistance in cancers, including in CC. Luciferase reporter assay confirmed the interaction between miR-4429 and RAD51. Finally, rescue assays indicated that miR-4429 promoted CC cell radio-sensitivity through RAD51. Consequently, our study showed that miR-4429 sensitized CC cells to irradiation by targeting RAD51, providing a potential therapeutic target for CC patients.
K E Y W O R D Scervical cancer, miR-4429, RAD51, radio-resistance
Brain ischemia and reperfusion (I/R) injury may lead to a poor prognosis for ischemic stroke, which could be alleviated by anti-oxidants with diminished oxidative stress. Betaine is a natural nutrient found in beetroot and seafood to improve cognitive performance in the elderly. The present study investigated whether betaine could protect the brain from I/R injury. Results showed that betaine treatment could reduce H2O2-induced cell death in the PC12 cell line. Pretreatment with betaine reduced the brain infarct volume and neuronal apoptosis in a rat I/R injury model induced by two-hour middle cerebral artery occlusion (MCAO). Biochemical analyses indicated that betaine treatment decreased pro-inflammatory cytokine production and reduced oxidative stress after I/R injury. Betaine increased the expression of anti-oxidative enzymes, such as glutathione peroxidase 4 (Gpx4) and superoxide dismutase 1 (Sod1), and anti-oxidative non-enzymatic genes, such as 3-mercaptopyruvate sulfurtransferase (Mpst), methionine sulfoxide reductases b1 (Msrb1), and Msrb2. These data suggest that betaine exerts a neuroprotective effect in I/R injury through enzymatic and non-enzymatic anti-oxidative systems and anti-inflammatory mechanisms.
β-patchoulene (β-PAE), an active constituent of the
Pogostemon cablin, is well known for its anti-inflammatory and antioxidative functions in various diseases. However, little is known about the impact of β-PAE on the cerebral ischemia-reperfusion (I/R) injury. The current study aimed to determine the
neuroprotective effect of β-PAE and the underlying mechanisms on cerebral I/R injury. Following pretreatment with β-PAE (10 mg/kg body weight) by tail intravenous injection for 1 h, Sprague-Dawley rats were subjected to middle cerebral artery occlusion for 2 h and reperfusion for 24 h. The results indicated that pretreatment with β-PAE could diminish the infarct volume, decrease the brain water content, reduce the neurological deficit score and restore the mitochondrial membrane potential, compared with the untreated I/R injury group. Furthermore, cell apoptosis was markedly suppressed by β-PAE, and this effect was associated with the decreased apoptosis regulator BAX/apoptosis regulator Bcl-2 expression ratio and caspase-3 activity. In addition, β-PAE significantly inhibited the release of proinflammatory factors, including tumor necrosis factor-α, interleukin (IL)-1β and IL-6. Superoxide generation and malondialdehyde levels were reduced while the levels of glutathione peroxidase and superoxide dismutase were elevated following treatment with β-PAE, indicating the antioxidative role of β-PAE in cerebral I/R injury. Furthermore, the Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathway was inhibited by β-PAE, as demonstrated by the decreased TLR4 expression and nuclear translocation of p65, and increased IκBα level. Taken together, the results suggested that β-PAE may exhibit a neuroprotective effect on cerebral I/R injury in rats through inactivating the TLR4/NF-κB signaling pathway.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.