Objective: Present study focused on the influence of lncRNA MALAT1 on coronary atherosclerotic heart disease (CAD) by regulating miR-15b-5p/ MAPK1 and mTOR signaling pathway. Method: Differentially expressed genes and activated pathway were investigated through bioinformatics analysis. QRT-PCR was conducted to verify expression of MALAT1 , miR-15b-5p and MAPK1 in CAD blood samples and endothelial progenitor cells (EPCs). In addition, the interactions among MALAT1 , miR-15b-5p and MAPK1 were revealed by Luciferase reporter assay. Cell autophagy of EPCs was examined by Cyto-ID Autophagy Detection Kit and transmission electron microscope. MTT assay and flow cytometry were carried out to assess cell viability and apoptosis in different interference conditions. Western blot was performed to testify the expression of pERK1/2 (MAPK1), phosphorylated mTOR, ATG1 and LC3-II. Vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) were detected by qRT-PCR. Finally, the effect of lncRNA MALAT1 on cell autophagy and atherogenesis was tested in vivo . Results: MALAT1 was overexpressed in CAD blood samples and EPCs. Knockdown of MALAT1 and MAPK1 promoted cell viability, autophagy and further suppressed the development of CAD. Antago MALAT1 protects mice against atherosclerosis. Conclusion: LncRNA MALAT1 inhibited EPCs autophagy and increased cell viability while repressed apoptosis of CAD via activating mTOR signaling pathway.

Glioblastoma (GBM) is the most malignant and lethal intracranial tumor, with extremely limited treatment options. Immunotherapy has been widely studied in GBM, but none can significantly prolong the overall survival (OS) of patients without selection. Considering that GBM cancer stem cells (CSCs) play a non-negligible role in tumorigenesis and chemoradiotherapy resistance, we proposed a novel stemness-based classification of GBM and screened out certain population more responsive to immunotherapy. The one-class logistic regression algorithm was used to calculate the stemness index (mRNAsi) of 518 GBM patients from The Cancer Genome Atlas (TCGA) database based on transcriptomics of GBM and pluripotent stem cells. Based on their stemness signature, GBM patients were divided into two subtypes via consensus clustering, and patients in Stemness Subtype I presented significantly better OS but poorer progression-free survival than Stemness Subtype II. Genomic variations revealed patients in Stemness Subtype I had higher somatic mutation loads and copy number alteration burdens. Additionally, two stemness subtypes had distinct tumor immune microenvironment patterns. Tumor Immune Dysfunction and Exclusion and subclass mapping analysis further demonstrated patients in Stemness Subtype I were more likely to respond to immunotherapy, especially anti-PD1 treatment. The pRRophetic algorithm also indicated patients in Stemness Subtype I were more resistant to temozolomide therapy. Finally, multiple machine learning algorithms were used to develop a 7-gene Stemness Subtype Predictor, which were further validated in two external independent GBM cohorts. This novel stemness-based classification could provide a promising prognostic predictor for GBM and may guide physicians in selecting potential responders for preferential use of immunotherapy.

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The results indicated that Grb1 can exert anti-HF function by inhibiting cardiomyocyte autophagy of rats through regulation of Rho/ROCK and PI3K/mTOR pathways.

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MicroRNAs are a class of small non-coding RNA molecules that play crucial roles in the initiation and progression of lung cancer. This study was undertaken to investigate the expression and roles of miR-186 in lung cancer. Ectopic expression experiments demonstrated that miR-186 functions as a tumor suppressor. Bioinformatic predictions, a luciferase reporter assay, and protein expression analysis suggested that miR-186 could inhibit the protein levels of SIRT6, a purported tumor suppressor gene. Collectively, our results indicated that miR-186 could inhibit lung cancer progression through targeting SIRT6 and that miR-186 may be a therapeutic target for lung cancer.

Glioblastoma (GBM) is a highly malignant brain tumor with a dismal prognosis. Standard therapy for GBM comprises surgical resection, followed by radiotherapy plus concomitant and adjuvant temozolomide (TMZ) therapy. The methylation status of the O6-methylguanine DNA methyltransferase (MGMT) promoter is one of the most essential predictive biomarkers for patients with GBM treated with TMZ. Patients with an unmethylated MGMT promoter (umMGMT), who comprise 60% of patients with GBM, present an even worse prognosis because of TMZ resistance. Radiotherapy with various fractionation, chemotherapy compensating for TMZ, targeted therapy against diverse oncogenic pathways, immunotherapy of vaccine or immune checkpoint inhibitor, and tumor treating fields have been studied in umMGMT GBM patients. However, most efforts have yielded negative results or merely minimal improvements. Therefore, effective patient subgroup selection concerning precision medicine has become the focus. By assigning different treatments to the corresponding patient subgroups, a better curative effect and subsequently prolonged survival can be achieved. In this review, we re-evaluate the value of standard TMZ therapy and summarize the new clinical strategies and attempts to treat patients with umMGMT, which yielded positive and negative results, to provide alternative treatment options and discuss future directions of umMGMT GBM treatment.