Showing papers by "Jing Liu published in 2020"

lncRNA LINC00665 Stabilized by TAF15 Impeded the Malignant Biological Behaviors of Glioma Cells via STAU1-Mediated mRNA Degradation

Abstract: Glioma is a brain cancer characterized by strong invasiveness with limited treatment options and poor prognosis. Recently, dysregulation of long non-coding RNAs (lncRNAs) has emerged as an important component in cellular processes and tumorigenesis. In this study, we demonstrated that TATA-box binding protein associated factor 15 (TAF15) and long intergenic non-protein coding RNA 665 (LINC00665) were both downregulated in glioma tissues and cells. TAF15 overexpression enhanced the stability of LINC00665, inhibiting malignant biological behaviors of glioma cells. Both metal regulatory transcription factor 1 (MTF1) and YY2 transcription factor (YY2) showed high expression levels in glioma tissues and cells, and their knockdown inhibited malignant progression. Mechanistically, overexpression of LINC00665 was confirmed to destabilize MTF1 and YY2 mRNA by interacting with STAU1, and knockdown of STAU1 could rescue the MTF1 and YY2 mRNA degradation caused by LINC00665 overexpression. G2 and S-phase expressed 1 (GTSE1) was identified as an oncogene in glioma, and knockdown of MTF1 or YY2 decreased the mRNA and protein expression levels of GTSE1 through direct binding to the GTSE1 promoter region. Our study highlights a key role of the TAF15/LINC00665/MTF1(YY2)/GTSE1 axis in modulating the malignant biological behaviors of glioma cells, suggesting novel mechanisms by which lncRNAs affect STAU1-mediated mRNA stability, which can inform new molecular therapies for glioma.

Elevated MicroRNA-326 Levels Regulate the IL-23/IL-23R/Th17 Cell Axis in Hashimoto's Thyroiditis by Targeting a Disintegrin and Metalloprotease 17.

Abstract: Background: MicroRNAs (miRNAs) are a class of critical epigenetic regulators involved in several autoimmune diseases. Our previous study reported an miR-326-induced increase in T helper (Th) 17 cells in a mouse model of Hashimoto's thyroiditis (HT), but the pathogenic effect of miR-326 in HT patients has not been verified. The goal of the present study was to explore the pathogenic role of miR-326 and its underlying molecular mechanism in HT patients. Methods: A total of 58 HT patients and 55 normal controls were enrolled in this study. We examined whether Th17 cells and miR-326 were aberrantly altered in the peripheral blood mononuclear cells (PBMCs) of HT patients with flow cytometry and real-time polymerase chain reaction. Levels of membrane interleukin (IL)-23R (mIL-23R) were determined by flow cytometry and Western blot to explore the critical role of mIL-23R in the development of Th17 cells. Isolated CD3+ T cells were used to further investigate the ectodomain shedding of mIL-23R by a disintegrin and metalloprotease (ADAM17). Furthermore, miR-326 inhibitor and mimics were transfected into PBMCs derived from HT patients and healthy controls to verify the regulation of ADAM17 by miR-326. Results: We observed elevated miR-326 levels in the PBMCs of HT patients compared with those in the PBMCs of healthy controls. Consistent with IL-23-induced STAT3 overactivation, substantially more HT patient-derived PBMCs differentiated into Th17 cells under polarization culture conditions, which may, at least in part, have resulted from enhanced mIL-23R levels. Furthermore, ADAM17, an ectodomain sheddase of mIL-23R, was targeted and negatively regulated by miR-326. Inhibiting ADAM17 might attenuate the ectodomain shedding of mIL-23R. Conclusions: Our findings suggest that the effect of miR-326 on the IL-23/IL-23R/Th17 cell axis in HT patients might be partially due to the targeting of ADAM17.

Nomogram-based prediction of survival in unresectable or metastatic gastric cancer patients with good performance status who received first-line chemotherapy

Abstract: Background Good performance status (PS) is widely acknowledged to have a high prognostic ability, although the prognostic parameters of cancer patients with good PS are still uncertain. This study was conducted to establish and validate a point-based nomogram to assist with predicting prognosis in unresectable or metastatic gastric cancer (GC) patients who had good PS and underwent first-line chemotherapy. Methods At random, a total of 309 patients with GC were split into 2 cohorts: a training cohort (n=259) and an internal validation cohort (n=50). An independent external validation cohort comprising 147 patients was also recruited. Both univariate and multivariate Cox regression analyses were used to evaluate patients based on the overall survival (OS) to develop the nomogram, which was subsequently validated using the concordance index (c-index), calibration curve, and decision curve analysis (DCA). Results The nomogram contained 3 independent prognostic variables in the training cohort: the number of distant metastatic sites (P<0.001), carbohydrate antigen 199 (CA199) level (P=0.002), and fibrinogen (P=0.020). The nomogram predicted an OS with a c-index of 0.623 (95% CI, 0.58-0.67) in the training cohort. The internal validation showed that the nomogram had a c-index of 0.614 (95% CI, 0.51-0.72). For external validation, the c-index was 0.638 (95% CI, 0.58-0.70). Conclusions A reliable point-based nomogram for predicting the prognosis of patients who had unresectable or metastatic GC and good PS who underwent first-line chemotherapy was developed and validated. Keywords Nomogram-based prediction; overall survival; unresectable gastric cancer; metastatic gastric cancer; good performance status; first-line chemotherapy.