ABSTRACT
Ubiquitin protein ligase E3 component n-recognin 5 (UBR5) has been identified as an oncogene in diverse cancers; however, whether its expression was associated with radiosensitivities of non-small cell lung cancer (NSCLC) cells remains unclear. Expression levels of UBR5 in NSCLC tissues and cell lines were examined by immunohistochemical staining and western blotting. Colony formation assay, CCK-8 cell viability assay, flow cytometry, and caspase-3 activity assay were performed to evaluate the radiosensitization of UBR5 knockdown in NSCLC cells, and the underlying mechanism in vitro was also investigated. UBR5 was highly expressed in NSCLC tissues, and its high expression was associated with the poor prognosis in 50 patients with NSCLC. After X-ray irradiation, the protein expression levels of UBR5 were also increased in NSCLC cells. UBR5 inhibition enhanced the radiosensitivity of NSCLC cells by inhibiting the cell viability and inducing apoptosis. Further investigation indicated that UBR5 knockdown-mediated radiosensitization involved the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway. Knockdown of UBR5 radiosensitizes NSCLC cells via the inactivation of the PI3K/AKT signal, which provided a novel therapeutic target for NSCLC radiosensitization.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Signal Transduction , Ubiquitin-Protein Ligases , Apoptosis , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/radiotherapy , Cell Line, Tumor , Cell Proliferation , Humans , Lung Neoplasms/genetics , Lung Neoplasms/radiotherapy , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Radiation Tolerance , Ubiquitin-Protein Ligases/geneticsABSTRACT
PURPOSE: Cervical cancer (CC) is the fourth most common cancer with high death rate in females. The study aims to detect the mechanism of long non-coding RNA (LncRNA) PCAT1 on radiosensitivity of CC. METHODS: The expression of PCAT1, miR-128 and GOLM1 in CC tissues and cells was measured by qRT-PCR. Different doses of X-ray were used for radiation treatment of CC cells and 6 Gy was chosen to perform the following experiments. The proliferation, migration and invasion of CC cells were measured by MTT assay, wound healing assay and transwell assay, respectively. The target relationships among PCAT1, miR-128 and GOLM1 were predicted by StarBase and TargetScan and verified by luciferase reporter assay. The protein level of GOLM1 was determined by Western blot. The xenograft tumor model was constructed in nude mice to verify the effect of PCAT1 on radiosensitivity of CC in vivo. RESULTS: The PCAT1 expression was upregulated in CC tissues and cells. PCAT1 silencing enhances radiosensitivity of CC cells on proliferation, migration and invasion. MiR-128 was the target of PCAT1 and was negatively regulated by PCAT1. Upregulation of miR-128 enhances radiosensitivity of CC cells on proliferation, migration and invasion. GOLM1 was a target of miR-128 and was negatively regulated by miR-128. Upregulation of GOLM1 and downregulation of miR-128 both reversed the enhanced effect of PCAT1 knockdown on radiosensitivity of CC cells, which partly promoted the proliferation, migration and invasion of CC cells. CONCLUSION: Silencing of PCAT1 enhanced radiosensitivity of CC via targeting miR-128/GOLM1, which provided a new idea for treating CC.
ABSTRACT
The utralow-temperature superplastic forging for sialon-based nanocomposites is reported for the first time. Sialon-based nanocomposites, with an average grain size smaller than 50 nm and 98.5% relative density, were prepared with nano-sized row powders by the spark plasma sintering (SPS) technique at a record ultralow sintering temperature of 1150 °C. An excellent gear is forged at the ultralow deformation temperature of 1200 °C with nanosized grains without any cracking. The maximum strain rate achieved is over 10-1 s-1, and a compression strain is more than 0.9. The practical application for superplastic forming of nitrogen ceramics is much more difficult than that for oxide ceramics because of the high deformation temperature and low strain rates. The present findings present a bright prospect for the near-net-shape superplastic forming of nitrogen ceramics.
