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Objective To explore the clinical significance of long non-coding RNA(lncRNA) VIM-AS5 expression in human breast cancer tissues and its regulatory mechanism involved in cancer cell proliferation and migration. Methods The Lnc2Cancer 3.0 database was used to analyze the expression of VIM-AS5 in breast cancer tissues and its correlation with the clinical stage and survival time of breast cancer patients. RT-qPCR was used to detect the expression of VIM-AS5 in breast cancer cell lines BT-549, MDA-MB-435, MDA-MB-231 and CAL-51. Plasmid with VIM-AS5 overexpression and negative control were all transfected into CAL-51 cells through liposome recorded as VIM-AS5 group and NC group, respectively. The proliferation and migration of CAL-51 cells were detected by colony formation assay and scratch healing method, respectively. Dual-luciferase reporter gene experiment verified the targeting relationship between VIM-AS5 and miR-500a. RT-qPCR was used to detect the expression of miR-500a in CAL-51 cells. Western blot was used to detect the expression of JAK/STAT3 pathway in CAL-51 cells. Results The expression of VIM-AS5 in breast cancer tissues was significantly lower than that in adjacent tissues(P＜0.01). VIM-AS5 expression was negatively correlated with the clinical stage of breast cancer patients(P＜0.01). The survival time of breast cancer patients with low VIM-AS5 expression was significantly shorter than that of breast cancer patients with high VIM-AS5 expression(P＜0.01). Compared with mammary epithelial cell line MCF-10A cells, VIM-AS5 expression was significantly reduced in breast cancer cells(P＜0.01). The counting number of colony formed in the VIM-AS5 group was significantly lower than that in the NC group(P＜0.01). The cell migration rate in the VIM-AS5 group was significantly lower than that in the NC group(P＜0.01). Dual-luciferase reporter gene experiment confirmed that miR-500a was the target gene of VIM-AS5(P＜0.01). VIM-AS5 can negatively regulate the expression of miR-500a(P＜0.01). Compared with the NC group, the expression of JAK/STAT3 pathway proteins JAK, p-STAT3, c-Myc, Bcl-2, and CDK3 in CAL-51 cells of the VIM-AS5 group were significantly decreased. Conclusions VIM-AS5 is low-expressed in breast cancer cells, and up-regulation of VIM-AS5 may inhibit the proliferation and migration of breast cancer cells CAL-51 by targeting at miR-500a/JAK/STAT3 pathway.

Objective To investigate the pharmacological process of the effect of rapamycin upon the proliferation of triple-negative breast cancer MDA-MB-231 cells by regulating tumor necrosis factor receptor-associated protein 1 （TRAP1），and to unravel the anti-breast cancer mechanism of rapamycin. Methods MDA-MB-231 cells were randomly divided into the control group and different-dose rapamycin groups，and then the effect of rapamycin on cell proliferation was detected by MTT assay at 24 h and 48 h，respectively. Meantime，the half-maximal inhibitory concentration （IC50） of rapamycin was considered as the research condition. The effect of rapamycin on MDA-MB-231 cell cycle was detected by flow cytometry. The expression levels of mammalian target of rapamycin （mTOR），p-mTOR and TRAP1 proteins were detected by Western blot. The expression levels of mTOR and TRAP1 mRNA were measured by qPCR. ATP content was detected by ATP kit. The amount of lactic acid was determined by lactate assay kit. Results Rapamycin inhibited the proliferation of MDA-MB-231 cells in a dose- and time-dependent manner （P < 0.01）. The proliferation of MDA-MB-231 cells was decreased at 24 h and significantly decreased at 48 h after rapamycin treatment. IC50 was obtained at 10 μmol/L after 48 h. Rapamycin induced cell cycle arrest at G1 phase （P < 0.01）. Compared with the control group，the expression level of TRAP1 mRNA was significantly down-regulated （P < 0.05），and the expression levels of p-mTOR and TRAP1 proteins were significantly down-regulated （both P < 0.001），whereas the expression levels of mTOR mRNA and total mTOR protein were not significantly changed （both P > 0.05），the content of ATP was significantly increased （P < 0.001），and the content of lactic acid was significantly decreased （P < 0.001） in the 48-h rapamycin group. Conclusion Rapamycin can inhibit the proliferation of MDA-MB-231 cells by regulating the metabolic process，which is related to the decrease of TRAP1.

The achievement of size uniformity and monodispersity in perovskite quantum dots (QDs) requires the implementation of precise temperature control and the establishment of optimal reaction conditions. Nevertheless, the accurate control of a range of reaction variables represents a considerable challenge. This study addresses the aforementioned challenge by employing manganese (Mn) doping to achieve size uniformity in CsPbBr3 perovskite QDs without the necessity for the precise control of the reaction conditions. By optimizing the Mn:Pb ratio, it is possible to successfully dope CsPbBr3 QDs with the appropriate concentrations of Mn²⁺ and achieve a uniform size distribution. The spectroscopic measurements on single QDs indicate that the appropriate Mn²⁺ concentrations can result in a narrower spectral linewidth, a longer photoluminescence (PL) lifetime, and a reduced biexciton Auger recombination rate, thus positively affecting the PL properties. This study not only simplifies the size control of perovskite QDs but also demonstrates the potential of Mn-doped CsPbBr3 QDs for narrow-linewidth light-emitting diode applications. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is the most common malignant diffuse glioma of the brain. Although immunotherapy with immune checkpoint inhibitors (ICIs), such as programmed cell death protein (PD)‐1/PD ligand‐1 inhibitors, has revolutionized the treatment of several cancers, the clinical benefit in GBM patients has been limited. Lymphocyte‐activation gene 3 (LAG‐3) binding to human leukocyte antigen‐II (HLA‐II) plays an essential role in triggering CD4+ T cell exhaustion and could interfere with the efficiency of anti‐PD‐1 treatment; however, the value of LAG‐3–HLA‐II interactions in ICI immunotherapy for GBM patients has not yet been analyzed. Therefore, we aimed to investigate the expression and regulation of HLA‐II in human GBM samples and the correlation with LAG‐3+CD4+ T cell infiltration. Human leukocyte antigen‐II was highly expressed in GBM and correlated with increased LAG‐3+CD4+ T cell infiltration in the stroma. Additionally, HLA‐IIHighLAG‐3High was associated with worse patient survival. Increased interleukin‐10 (IL‐10) expression was observed in GBM, which was correlated with high levels of HLA‐II and LAG‐3+ T cell infiltration in stroma. HLA‐IIHighIL‐10High GBM associated with LAG‐3+ T cells infiltration synergistically showed shorter overall survival in patients. Combined anti‐LAG‐3 and anti‐IL‐10 treatment inhibited tumor growth in a mouse brain GL261 tumor model. In vitro, CD68+ macrophages upregulated HLA‐II expression in GBM cells through tumor necrosis factor‐α (TNF‐α). Blocking TNF‐α‐dependent inflammation inhibited tumor growth in a mouse GBM model. In summary, T cell–tumor cell interactions, such as LAG‐3–HLA‐II, could confer an immunosuppressive environment in human GBM, leading to poor prognosis in patients. Therefore, targeting the LAG‐3–HLA‐II interaction could be beneficial in ICI immunotherapy to improve the clinical outcome of GBM patients. [ABSTRACT FROM AUTHOR]