Shepardwelch3170

Enforced expression of miR-1193 inhibited CC cell proliferation, invasion and migration. Mechanistically, we confirmed CLDN7 as a target of miR-1193, and restoration of CLDN7 robustly rescued the tumor suppressing effects of miR-1193 in CC cells. CLDN7 was upregulated in abnormal cervical tissues and its expression exhibited inverse correlation with that of miR-1193 in CC. Conclusion Our results suggested that miR-1193 exerted tumor inhibitory roles in CC malignancy by directly targeting CLDN7.Purpose Risk stratification in patients with multiple myeloma (MM) remains a challenge. As clinicopathological characteristics have been demonstrated insufficient for exactly defining MM risk, and molecular biomarkers have become the focuses of interests. Prognostic predictions based on gene expression profiles (GEPs) have been the most accurate to this day. The purpose of our study was to construct a risk score based on stemness genes to evaluate the prognosis in MM. Materials and methods Bioinformatics studies by ingenuity pathway analyses in side population (SP) and non-SP (MP) cells of MM patients were performed. Firstly, co-expression network was built to confirm hub genes associated with the top five Kyoto Encyclopedia of Genes and Genomes pathways. Functional analyses of hub genes were used to confirm the biologic functions. Next, these selective genes were utilized for construction of prognostic model, and this model was validated in independent testing sets. Finally, five stemness genes (ROCK1, GSK3B, BRAF, MAPK1 and MAPK14) were used to build a MM side population 5 (MMSP5) gene model, which was demonstrated to be forcefully prognostic compared to usual clinical prognostic parameters by multivariate cox analysis. MM patients in MMSP5 low-risk group were significantly related to better prognosis than those in high-risk group in independent testing sets. Conclusion Our study provided proof-of-concept that MMSP5 model can be adopted to evaluate recurrence risk and clinical outcome for MM. The MMSP5 model evaluated in different databases clearly indicated novel risk stratification for personalized anti-MM treatments.Purpose H2A.Z is an oncogenic histone variant that is overexpressed in cancers. Two isoforms of H2A.Z, H2AFZ and H2AFV, are identical except for a three-amino acid difference. However, their isoform-specific functions remain unclear in cancer development. Thereby, this study aimed to investigate whether the two isoforms play distinct functions in hepatocarcinogenesis. Materials and methods Expressions of H2A.Z isoforms in 116 paired hepatocellular cancerous and para-cancerous tissues were detected by employing qPCR. GEO and TCGA databases were used to probe expressions and prognostic value of the two H2A.Z isoforms. A comprehensive meta-analysis was conducted. Furthermore, co-expressed analysis of H2AFZ and H2AFV was performed by using cBioPortal database. H2A.Z binding genes from Chip-seq were intersected with H2A.Z isoforms co-expressed genes to perform functional annotations. Cell proliferation experiments from H2AFZ knockout HepG2 and BEL-7402 cells were implemented. Finally, RNA-seq was applied to analyse alternative splicing in H2AFZ knockout and wild-type cells. Results H2AFZ and H2AFV were both significantly upregulated (P less then 0.01) in hepatocellular carcinoma and related to poor prognosis (P less then 0.01). The two H2A.Z isoforms played vital roles in cell proliferation. It is also predicted that unique functions of H2AFV contain spindle midzone and microtubule, while H2AFZ is especially associated with RNA export and spliceosome. Further, devoid H2AFZ may restrain liver cancer cell proliferation and cause many alternative splicing events. Conclusion Both H2A.Z isoforms play vital and distinct roles in the occurrence and progression of liver cancer, which may pave a way for novel therapeutic applications for cancers in the future.Background Long non-coding RNAs (lncRNAs) play an imperative role in tumorigenesis, but few lncRNAs have been functionally characterized in glioma. The aim of the present study was to identify the role of long non-coding RNA LINC01614 (LINC01614) in glioma development and explore the underlying mechanisms of LINC01614/miR-383/ADAM12 axis. Patients and methods LncRNA expression in glioma specimens was measured by lncRNA microarray and qRT-PCR. The prognostic value of LINC01614 expression was statistically analyzed in 112 glioma patients. Loss-of-function experiments were conducted to investigate the biological functions of LINC01614 in vitro. Luciferase analyses, ChIP assays, and RNA pull-down were performed to determine the underlying LINC01614 mechanisms. Results We identified a novel glioma-related lncRNA LINC01614 by analyzing TCGA datasets. The distinct upregulation of LINC01614 was observed in both glioma specimens and cell lines using RT-PCR. We also observed that LINC01614 upregulation was induced by nuclear transcription factor SP1. Clinical assays revealed that high levels of LINC01614 were associated with KPS, WHO grade and shorter overall survival of glioma patients. Multivariate analysis further confirmed that LINC01614 was an independent prognostic marker for glioma patients. Besides, functional assays displayed that silence of LINC01614 knockdown distinctly inhibited cell growth, migration and invasion and promoted cell apoptosis in glioma cells. LINC01614 expression was enriched in the cytoplasm of glioma cells. Mechanistic investigation revealed that LINC01614 functioned as a competing endogenous RNA to upregulate a disintegrin and metalloproteinase 12 (ADAM12) by sponging miR-383. Conclusion Overall, these findings showed that SP1-induced upregulation of LINC01614 promoted glioma malignant progression via modulating the miR-383/ADAM12 axis, which may provide a promising therapy for glioma.Diffuse large B-cell lymphoma (DLBCL) is a complex and aggressive malignancy originating from B lymphocytes and characterized by extensive clinical, phenotypic and molecular heterogeneity. Cobimetinib Although research conducted over the past decades has substantially improved our understanding of DLBCL, its pathogenesis has not yet been fully elucidated. The development of RNA sequencing technology has allowed the identification of numerous long noncoding RNAs (lncRNAs) that exhibit aberrant expression in DLBCL. These lncRNAs play crucial roles in DLBCL development and pathogenesis and are thus good candidates for use as diagnostic biomarkers or therapeutic targets. In this review, we describe the lncRNAs associated with DLBCL, summarize their characteristics and molecular functions, and discuss their relationships with clinical practice.Background Colorectal cancer (CRC) is the most common cause of cancer-related mortality in the world. Long non-coding RNAs (lncRNAs) are involved in the development of many cancers. However, studies on the effect of lncRNA small nucleolar RNA host gene 16 (SNHG16) on the proliferation, metastasis and apoptosis of CRC are still few. Methods Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to determine the expression levels of SNHG16, microRNA-132-3p (miR-132-3p) and ubiquitin specific peptidase 22 (USP22). The proliferation, apoptosis, migration and invasion of CRC cells were evaluated by the 3-(4,5-dimethyl-2 thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, flow cytometry and transwell assay, respectively. Dual-luciferase reporter assay was used to verify the interactions among SNHG16, miR-132-3p and USP22. Also, Western blot analysis was used to assess the protein levels of USP22 and metastasis-related markers. Moreover, mice xenograft models were used to determine the effect of SNHG16 on CRC tumor growth in vivo. Results SNHG16 was highly expressed in CRC tissues and cells. Knockdown of SNHG16 reduced the proliferation, migration, invasion, and promoted the apoptosis of CRC cells. MiR-132-3p could interact with SNHG16, and its inhibitor recovered the suppression effect of silenced SNHG16 on CRC cell progression. Besides, USP22 was a target of miR-132-3p, and its overexpression restored the inhibition effect of miR-132-3p mimic on CRC cell progression. In addition, interference of SNHG16 reduced CRC tumor growth in vivo. Conclusion LncRNA SNHG16 might act as an oncogene in CRC. The discovery of the SNHG16/miR-132-3p/USP22 pathway provided new thinking for the treatment of CRC.Purpose To construct a competing endogenous RNA (ceRNA) topology network of RNA-seq data and micro RNA-seq (miRNA-seq) data to identify key prognostic long non-coding RNA (lncRNAs) in luminal breast cancer, and validate the results by human luminal breast cancer samples. Materials and methods The RNA-seq data and miRNA-seq data of luminal A breast cancer in the The Cancer Genome Atlas (TCGA) database were downloaded and compared with those in the miRcode database to obtain lncRNA-miRNA relationship pairs. Final target genes were predicted by all three databases (miRDB, miRTarBase, and TargetScan), thereby obtaining the miRNA-messenger RNA (miRNA-mRNA) relationship pairs and a ceRNA topology network was constructed, then mRNA enrichment analysis, ceRNA topological and stability analysis, univariate and multivariate Cox regression analysis were performed. Overall survival (OS) was evaluated and the key prognostic RNAs were identified. The expression difference between normal and tumor, as well as the correlation of high expression in tumor with pathological parameters (Ki-67, Grade, tumor diameter) were validated by human breast cancer specimens. Results A ceRNA topology network was constructed and six lncRNAs were finally identified (The higher expression of PART1, IGF2.AS, WT1.AS, OIP5.AS1, and SLC25A5.AS1 was associated with poor prognosis while AL035706.1 was adverse) and the poor prognostic ones were higher expressed in tumor tissue and correlated with a higher Ki-67 (>10%), tumor grades (II, III) and tumor diameters (>1.5 cm). Using six lncRNAs, we constructed a prognostic model, which performed well for the classification of prognosis in the module. Conclusion We identified and verified six biomarkers (OS-predicting) in luminal breast cancer, which significantly enriched the prediction and potential targets of this subtype.Purpose MicroRNA-939 (miR-939) has crucial roles in several types of human cancer. However, the expression profile and precise functions of miR-939 in prostate cancer (PCa) are still unclear. This study aimed to determine miR-939 expression in PCa and explore its roles in PCa tumorigenesis. Methods miR-939 expression was determined in PCa tissues and cell lines using reverse transcription-quantitative polymerase chain reaction. Cell Counting Kit-8, colony formation, and flow cytometric assays were used to determine the role of miR-939 in PCa cell proliferation and apoptosis in vitro, whereas a tumor xenograft model was generated to evaluate the effect of miR-939 on tumor growth in vivo. Transwell assays were performed to investigate whether miR-939 affects the migration and invasiveness of PCa cells. Results miR-939 was found to be downregulated in PCa tissues and cell lines, and this downregulation was significantly correlated with tumor stage and lymphatic metastasis. Patients with PCa exhibiting low miR-939 expression had shorter overall survival than those exhibiting high miR-939 expression.