Glioma is one of the most common primary malignancies of the central nervous system, which has aggressive clinical behavior and a poorer prognosis. MicroRNAs (miRs) are a class of small noncoding RNAs that function as mediators of gene expression, which can be sponged by circRNA provided with a closed circular structure. Dysregulations of circular RNAs (circRNAs) and miRs have been implicated in the development and progression of glioma. In the current study, we investigated the role of circular RNA hsa_circ_0076248 in mediating the oncogenesis of glioma by sponging miR‐181a to modulate silent information regulator 1 (SIRT1) expression in vitro and in vivo. The quantitative real‐time polymerase chain reaction results showed that the expression of miR‐181a was significantly decreased in glioma tissues and cell lines compared with normal brain tissues and normal gliocyte, respectively, and the expression of hsa_circ_0076248 and SIRT1 demonstrated the opposite. Bioinformatics analysis identified hsa_circ_0076248 could sponge miR‐181a, and miR‐181a could target the mRNA of SIRT1. Our results verified that downregulating hsa_circ_0076248 or upregulating miR‐181a could depress the proliferation and invasion of glioma in vitro and in vivo. The experiment also showed that downregulating hsa_circ_0076248 or upregulating miR‐181a could remarkably promote the temozolomide chemotherapy sensitivity. Furthermore, Western blot analysis testified that downregulating hsa_circ_0076248 or upregulating miR‐181a could promote the expression of p53 and SIRT1. In summary, our study sheds light on the regulatory mechanism of hsa_circ_0076248 in glioma growth and invasion via sponging miR‐181a, which downregulates the SIRT1 expression and also suggests that hsa_circ_0076248, miR‐181a, and SIRT1 may serve as potential therapeutic targets for glioma.

Background: Lung cancer is the most aggressive cancer, resulting in one-quarter of all cancerrelated deaths, and its metastatic spread accounts for >70% of these deaths, especially metastasis to the brain. Metastasis-associated mutations are important biomarkers for metastasis prediction and outcome improvement.Methods: In this study, we applied whole-exome sequencing (WES) to identify potential metastasis-related mutations in 12 paired lung cancer and brain metastasis samples. Results:We identified 1,702 single nucleotide variants (SNVs) and 6,131 mutation events among 1,220 genes. Furthermore, we identified several lung cancer metastases associated genes (KMT2C, AHNAK2).A mean of 3.1 driver gene mutation events per tumor with the dN/dS (non-synonymous substitution rate/ synonymous substitution rate) of 2.13 indicating a significant enrichment for cancer driver gene mutations.Mutation spectrum analysis found lung-brain metastasis samples have a more similar Ti/Tv (transition/ transversion) profile with brain cancer in which C to T transitions are more frequent while lung cancer has more C to A transversion. We also found the most important tumor onset and metastasis pathways, such as chronic myeloid leukemia, ErbB signaling pathway, and glioma pathway. Finally, we identified a significant survival associated mutation gene ERF in both The Cancer Genome Atlas (TCGA) (P=0.01) and our dataset (P=0.012). Conclusions:In summary, we conducted a pairwise lung-brain metastasis based exome-wide sequencing and identified some novel metastasis-related mutations which provided potential biomarkers for prognosis and targeted therapeutics.

Armadillo repeat-containing proteins (ARMCs) are widely distributed in eukaryotes and have important influences on cell adhesion, signal transduction, mitochondrial function regulation, tumorigenesis, and other processes. These proteins share a similar domain consisting of tandem repeats approximately 42 amino acids in length, and this domain constitutes a substantial platform for the binding between ARMCs and other proteins. An ARMC subfamily, including ARMC1∼10, ARMC12, and ARMCX1∼6, has received increasing attention. These proteins may have many terminal regions and play a critical role in various diseases. On the one hand, based on their similar central domain of tandem repeats, this ARMC subfamily may function similarly to other ARMCs. On the other hand, the unique domains on their terminals may cause these proteins to have different functions. Here, we focus on the ARMC subfamily (ARMC1∼10, ARMC12, and ARMCX1∼6), which is relatively conserved in vertebrates and highly conserved in mammals, particularly primates. We review the structures, biological functions, evolutions, interactions, and related diseases of the ARMC subfamily, which involve more than 30 diseases and 40 bypasses, including interactions and relationships between more than 100 proteins and signaling molecules. We look forward to obtaining a clearer understanding of the ARMC subfamily to facilitate further in-depth research and treatment of related diseases.