A short peptide LINC00665_18aa encoded by lncRNA LINC00665 suppresses the proliferation and migration of osteosarcoma cells through the regulation of the CREB1/RPS6KA3 interaction.

Long noncoding RNAs (lncRNAs) encompass short open reading frames (sORFs) that can be translated into small peptides. Here, we investigated the encoding potential of lncRNA LINC00665 in osteosarcoma (OS) cells. Bioinformatic analyses were utilized to predict the lncRNAs with encoding potential in human U2OS cells. Protein expression was assessed by an immunoblotting or immunofluorescence method. Cell viability was assessed by cell counting Kit-8 (CCK-8). Cell proliferation was detected by 5-ethynyl-2'-deoxyuridine (EdU) assay. Cell migration was gauged by transwell assay. The downstream effectors of the short peptide were verified using qualitative proteome analysis after immunoprecipitation (IP) experiments. The effect of the short peptide on protein interactions were confirmed by Co-Immunoprecipitation (CoIP) assays. We found that lncRNA LINC00665 encoded an 18-amino acid (aa)-long short peptide (named LINC00665_18aa). LINC00665_18aa suppressed the viability, proliferation, and migration of human MNNG-HOS and U2OS OS cells in vitro and diminished tumor growth in vivo. Mechanistically, LINC00665_18aa impaired the transcriptional activity, nuclear localization, and phosphorylation of cAMP response element-binding protein 1 (CREB1). Moreover, LINC00665_18aa weakened the interaction between CREB1 and ribosomal protein S6 kinase A3 (RPS6KA3, RSK2). Additionally, increased expression of CREB1 reversed the inhibitory effects of LINC00665_18aa on OS cell proliferation and migration. Our findings show that the short peptide LINC00665_18aa exerts a tumor-inhibitory function in OS, providing a new basis for cancer therapeutics through the functions of the short peptides encoded by lncRNAs.

Prognostic value of preoperative hematological markers in patients with glioblastoma multiforme and construction of random survival forest model.

OBJECTIVE: In recent years, an increasing number of studies have revealed that patients' preoperative inflammatory response, coagulation function, and nutritional status are all linked to the occurrence, development, angiogenesis, and metastasis of various malignant tumors. The goal of this study is to determine the relationship between preoperative peripheral blood neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR), systemic immune-inflammatory index (SII), platelet to lymphocyte ratio (PLR), and platelet to fibrinogen ratio (FPR). Prognostic nutritional index (PNI) and the prognosis of glioblastoma multiforme (GBM) patients, as well as establish a forest prediction model that includes preoperative hematological markers to predict the individual GBM patient's 3-year survival status after treatment. METHODS: The clinical and hematological data of 281 GBM patients were analyzed retrospectively; overall survival (OS) was the primary endpoint. X-Tile software was used to determine the best cut-off values for NLR, SII, and PLR, and the survival analysis was carried out by the Kaplan-Meier method as well as univariate and multivariate COX regression. Afterward, we created a random forest model that predicts the individual GBM patient's 3-year survival status after treatment, and the area under the curve (AUC) is used to validate the model's effectiveness. RESULTS: The best cut-off values for NLR, SII, and PLR in GBM patients' preoperative peripheral blood were 2.12, 537.50, and 93.5 respectively. The Kaplan-Meier method revealed that preoperative GBM patients with high SII, high NLR, and high PLR had shorter overall survival, and the difference was statistically significant. In addition to clinical and pathological factors. Univariate Cox showed NLR (HR = 1.456, 95% CI: 1.286 ~ 1.649, P < 0.001) MLR (HR = 1.272, 95% CI: 1.120 ~ 1.649, P < 0.001), FPR (HR = 1.183,95% CI: 1.049 ~ 1.333, P < 0.001), SII (HR = 0.218,95% CI: 1.645 ~ 2.127, P < 0.001) is related to the prognosis and overall survival of GBM. Multivariate Cox proportional hazard regression showed that SII (HR = 1.641, 95% CI: 1.430 ~ 1.884, P < 0.001) is also related to the overall survival of patients with GBM. In the random forest prognostic model with preoperative hematologic markers, the AUC in the test set and the validation set was 0.907 and 0.900, respectively. CONCLUSION: High levels of NLR, MLR, PLR, FPR, and SII before surgery are prognostic risk factors for GBM patients. A high preoperative SII level is an independent risk factor for GBM prognosis. The random forest model that includes preoperative hematological markers has the potential to predict the individual GBM patient's 3-year survival status after treatment,and assist the clinicians for making a good clinical decision.

Comparison of pedicle screw-based dynamic stabilization and fusion surgery in the treatment of radiographic adjacent-segment degeneration: a retrospective analysis of single L5-S1 degenerative spondylosis covering 4 years.

OBJECTIVE Pedicle screw-based dynamic spinal stabilization systems (PDSs) were devised to decrease, theoretically, the risk of long-term complications such as adjacent-segment degeneration (ASD) after lumbar fusion surgery. However, to date, there have been few studies that fully proved that a PDS can reduce the risk of ASD. The purpose of this study was to examine whether a PDS can influence the incidence of ASD and to discuss the surgical coping strategy for L5-S1 segmental spondylosis with preexisting L4-5 degeneration with no related symptoms or signs. METHODS This study retrospectively compared 62 cases of L5-S1 segmental spondylosis in patients who underwent posterior lumbar interbody fusion (n = 31) or K-Rod dynamic stabilization (n = 31) with a minimum of 4 years' follow-up. The authors measured the intervertebral heights and spinopelvic parameters on standing lateral radiographs and evaluated preexisting ASD on preoperative MR images using the modified Pfirrmann grading system. Radiographic ASD was evaluated according to the results of radiography during follow-up. RESULTS All 62 patients achieved remission of their neurological symptoms without surgical complications. The Kaplan-Meier curve and Cox proportional-hazards model showed no statistically significant differences between the 2 surgical groups in the incidence of radiographic ASD (p > 0.05). In contrast, the incidence of radiographic ASD was 8.75 times (95% CI 1.955-39.140; p = 0.005) higher in the patients with a preoperative modified Pfirrmann grade higher than 3 than it was in patients with a modified Pfirrmann grade of 3 or lower. In addition, no statistical significance was found for other risk factors such as age, sex, and spinopelvic parameters. CONCLUSIONS Pedicle screw-based dynamic spinal stabilization systems were not found to be superior to posterior lumbar interbody fusion in preventing radiographic ASD (L4-5) during the midterm follow-up. Preexisting ASD with a modified Pfirrmann grade higher than 3 was a risk factor for radiographic ASD. In the treatment of degenerative diseases of the lumbosacral spine, the authors found that both of these methods are feasible. Also, the authors believe that no extra treatment, other than observation, is needed for preexisting degeneration in L4-5 without any clinical symptoms or signs.