LncRNA ANRIL promotes multiple myeloma progression and bortezomib resistance by EZH2-mediated epigenetically silencing of PTEN.

Multiple myeloma (MM) is a plasma cell malignancy of bone marrow. In the present study, we aimed to study the function and potential mechanism of the antisense non-coding RNA in the INK4 Locus (ANRIL) in MM. The expression levels of ANRIL in MM patients and healthy donors were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). The effects and mechanisms of ANRIL in MM were evaluated by cell viability assay, BrdU incorporation assay, tumor xenograft model, flow cytometry, western blot, RNA immunoprecipitation (RIP), transcriptome RNA sequencing, and chromatin immunoprecipitation (ChIP). We found that ANRIL was upregulated in MM patients and cell lines, and associated with advanced international staging system (ISS) stage and poor overall survival. Enforced ANRIL expression promoted proliferation and tumor xenograft growth of MM cells, while knockdown of ANRIL exhibited opposite effects. Moreover, ANRIL overexpression increased the half-maximal inhibitory concentration (IC50) of bortezomib and reduced bortezomib-induced apoptosis in MM cells. ANRIL was found to accumulate in the nuclei of MM cells, and interact with EZH2 by RIP assay. Transcriptome RNA sequencing identified PTEN as a target of ANRIL in MM cells. In the ChIP assay, knockdown of ANRIL reduced EZH2 occupancy and H3K27me3 binding to the promoter region of PTEN. Furthermore, EZH2 knockout or PTEN restoration abrogated the effects caused by ANRIL overexpression in MM cells. Our results indicated that ANRIL exerted oncogenic functions and conferred chemoresistance of MM cells by EZH2-mediated epigenetically silencing of PTEN.

Lumbar decompression and lumbar interbody fusion in the treatment of lumbar spinal stenosis: A systematic review and meta-analysis.

BACKGROUND: The goal of this study was to review relevant randomized controlled trials in order to determine the efficacy of decompression and lumbar interbody fusion in the treatment of lumbar spinal stenosis. METHOD: Using appropriate keywords, we identified relevant studies in PubMed, the Cochrane library, and Embase. Key pertinent sources in the literature were also reviewed, and all articles published through July 2019 were considered for inclusion. For each study, we assessed odds ratios, mean difference, and 95% confidence interval to assess and synthesize outcomes. RESULT: Twenty-one randomized controlled trials were eligible for this meta-analysis with a total of 3636 patients. Compared with decompression, decompression and fusion significantly increased length of hospital stay, operative time and estimated blood loss. Compared with fusion, decompression significantly decreased operative time, estimated blood loss and overall visual analogue scale (VAS) scores. Compared with endoscopic decompression, microscopic decompression significantly increased length of hospital stay, and operative time. Compared with traditional surgery, endoscopic discectomy significantly decreased length of hospital stay, operative time, estimated blood loss, and overall VAS scores and increased Japanese Orthopeadic Association score. Compared with TLIF, MIS-TLIF significantly decreased length of hospital stay, and increased operative time and SF-36 physical component summary score. Compared with multi-level decompression and single level fusion, multi-level decompression and multi-level fusion significantly increased operative time, estimated blood loss and SF-36 mental component summary score and decreased Oswestry disability index score. Compared with decompression, decompression with interlaminar stabilization significantly decreased operative time and the score of Zurich claudication questionnaire symptom severity, and increased VAS score. CONCLUSION: Considering the limited number of included studies, we still need larger-sample, high-quality, long-term studies to explore the optimal therapy for lumbar spinal stenosis.