ABSTRACT
INTRODUCTION: Uveal melanoma is one of the most common primary intraocular malignant tumors with poor prognosis and limited treatments. Programmed cell death receptor-1 (PD-1) blockade represents the primary treatment strategy of immune checkpoint inhibition; however, there is a lack of studies on whether PD-1 expression in primary (ocular) uveal melanoma affects tumor progression. METHODS: PD-1 expression in 82 cases of primary (ocular) uveal melanoma was detected by immunohistochemistry. The clinical significance of PD-1 expression was evaluated using univariate and multivariate analysis. PD-1 overexpression and knockdown studies were conducted in C918 and Mum-2B cell lines to analyze the effect of PD-1 expression on tumor cell proliferation and intracellular cell signaling transduction. real-time qPCR (RT-qPCR) and western blot analysis were performed to investigate the gene expression level. CCK8 assays were performed to examine the cell proliferation ability. RESULTS: High expression of primary (ocular) intratumor PD-1 was associated with poor patient survival. Moreover, PD-1 expression was correlated with the largest tumor diameter. PD-1 expression and optic nerve invasion were independent prognostic risk factors. PD-1 overexpression in uveal melanoma cell lines promoted tumor cell proliferation, while knockdown of PD-1 inhibited cell proliferation capacity. CONCLUSION: Our study established the role of PD-1 in the progression of uveal melanoma and provided a new potential treatment selection for uveal melanoma.
Subject(s)
Melanoma/metabolism , Programmed Cell Death 1 Receptor/biosynthesis , Uveal Neoplasms/metabolism , Analysis of Variance , Cell Proliferation/physiology , Female , Humans , Immunohistochemistry , Male , Melanoma/genetics , Melanoma/pathology , Middle Aged , Prognosis , Programmed Cell Death 1 Receptor/genetics , Programmed Cell Death 1 Receptor/metabolism , Signal Transduction , Survival Analysis , TOR Serine-Threonine Kinases/metabolism , Uveal Neoplasms/genetics , Uveal Neoplasms/pathologyABSTRACT
PURPOSE: The indispensable role of long non-coding RNAs (lncRNAs) in tumorigenesis has been increasingly reported. In the present study, LINC01694 was found to regulate the proliferation, invasion, as well as apoptosis in gallbladder cancer (GBC) cells through sponging miR-340-5p. METHODS: LINC01694 level in GBC cells was quantified by quantitative real-time polymerase chain reaction (qRT-PCR). The proliferation, invasion, and apoptosis were determined by Cell Counting Kit-8 (CCK-8), Transwell, and flow cytometry, respectively. The expression of Sry-related high-mobility group box 4 (Sox4) was detected by Western blot (WB). The interaction between LINC01694 and miR-340-5p was measured by dual-luciferase reporter (DLR) assay, RNA immunoprecipitation (RIP) test, and RNA pull-down. Tumor formation was examined by in vivo experiment. RESULTS: qRT-PCR illustrated that cancerous tissues had higher LINC01694 than normal tissues. Survival analysis demonstrated that the prognosis of patients with high LINC01694 was significantly poorer than those with low LINC01694. Down-regulation of LINC01694 slowed down the proliferation and invasion in GBC cells and accelerated the apoptosis. DLR assay indicated that LINC01694 elevated Sox4 expression by regulating miR-340-5p. LINC01694 functioned as miR-340-5p sponge to inhibit Sox4 expression. CONCLUSION: LINC01694 level is elevated in GBC by regulating miR-340-5p/Sox4 axis, which indicates the poor prognosis of the patients.
Subject(s)
Gallbladder Neoplasms/genetics , Gene Expression Regulation, Neoplastic , MicroRNAs/metabolism , RNA, Long Noncoding/metabolism , SOXC Transcription Factors/genetics , Animals , Apoptosis/genetics , Case-Control Studies , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Cholecystectomy , Datasets as Topic , Female , Gallbladder/pathology , Gallbladder/surgery , Gallbladder Neoplasms/pathology , Gallbladder Neoplasms/surgery , Gene Knockdown Techniques , Healthy Volunteers , Humans , Male , Mice , Middle Aged , RNA, Long Noncoding/genetics , Xenograft Model Antitumor AssaysABSTRACT
The aim of the present study was to examine the effect of fraxetin on proliferation and apoptosis in the MCF-7 breast cancer cell line. Cell proliferation was measused using an MTT assay and 4',6-diamidino-2-phenylindole (DAPI) staining was used to determine shrinkage and condensation. RT-PCR was used to examine the expression of factor-associated suicide (Fas) and Fas ligand (FasL) mRNA, and western blot analysis was used to examine Bax and Bcl-2 protein. MTT showed that the proliferation of MCF-7 cells was significantly inhibited by fraxetin in a dose-dependent manner. Fraxetin also induced significant morphological changes of MCF-7 cells, suggestive of apoptosis, whereas DAPI staining showed that fraxetin caused cell shrinkage and chromatin condensation. RT-PCR showed that the expression of Fas and FasL mRNA was upregulated by fraxetin and the western blot analysis revealed that Bax was upregulated and Bcl-2 was downregulated. In conclusion, fraxetin can inhibit the proliferation of MCF-7 cells, induce apoptosis, upregulate Fas, FasL and Bax, and downregulate Bcl-2 to induce apoptosis. These results support the potential therapeutic role for fraxetin in breast cancer.
ABSTRACT
The anisotropic thermal-conductivity tensor of bulk black phosphorus (BP) for 80 ≤T ≤ 300 K is reported. Despite the anisotropy, phonons are predominantly scattered by Umklapp processes in all the crystallographic orientations. It is also found that the phonon mean-free-paths of BP are rather long (up to 1 µm) in the through-plane direction.
