The long noncoding RNA HOTAIRM1 controlled by AML1 enhances glucocorticoid resistance by activating RHOA/ROCK1 pathway through suppressing ARHGAP18.

Acquired resistance to glucocorticoids (GCs) is an obstacle to the effective treatment of leukemia, but the molecular mechanisms of steroid insensitivity have not been fully elucidated. In this study, we established an acquired GC-resistant leukemia cell model and found a long noncoding RNA, HOTAIRM1, was overexpressed in the resistant cells by transcriptional profiling, and was higher expressed in patients with poor prognosis. The whole-genome-binding sites of HOTAIRM1 were determined by ChIRP-seq (chromatin isolation by RNA purification combined with sequencing) analysis.

Heterogeneous Nuclear Ribonucleoprotein A1 Loads Batched Tumor-Promoting MicroRNAs Into Small Extracellular Vesicles With the Assist of Caveolin-1 in A549 Cells.

MicroRNAs in small extracellular vesicle (sEV-miRNAs) have been widely investigated as crucial regulated molecules secreted by tumor cells to communicate with surroundings. It is of great significance to explore the loading mechanism of sEV-miRNAs by tumor cells. Here, we comprehensively illustrated a reasoned loading pathway of batched tumor-promoting sEV-miRNAs in non-small cell lung cancer (NSCLC) cell line A549 with the application of a multi-omics method.

Identification of Potential Key lncRNAs in the Context of Mouse Myeloid Differentiation by Systematic Transcriptomics Analysis.

Hematopoietic differentiation is a well-orchestrated process by many regulators such as transcription factor and long non-coding RNAs (lncRNAs). However, due to the large number of lncRNAs and the difficulty in determining their roles, the study of lncRNAs is a considerable challenge in hematopoietic differentiation. Here, through gene co-expression network analysis over RNA-seq data generated from representative types of mouse myeloid cells, we obtained a catalog of potential key lncRNAs in the context of mouse myeloid differentiation.

-- regulates cognitive functions in the hippocampus through complement component 3-dependent modulation of synaptic vesicle release.

microRNA-218 (miR-218) has been linked to several cognition related neurodegenerative and neuropsychiatric disorders. However, whether miR-218 plays a direct role in cognitive functions remains unknown. Here, using the miR-218 knockout (KO) mouse model and the sponge/overexpression approaches, we showed that -- but not -- could bidirectionally regulate the contextual and spatial memory in the mice.

Secretome of Activated Fibroblasts Induced by Exosomes for the Discovery of Biomarkers in Non-Small Cell Lung Cancer.

Molecules involved in crosstalk between tumor cells and fibroblasts play vital roles in tumor progression. Extracellular matrix proteins, whose abundance is altered after being affected by tumor-derived exosomes, possess considerable promise as biomarkers for diagnosis or prognosis. In this study, quantitative proteomics is employed to determine the abundance of proteins secreted by normal fibroblasts and exosome-activated fibroblasts, which first identify differentially secreted proteins affected by lung cancer cell-derived exosomes.

A promising iPS-based single-cell cloning strategy revealing signatures of somatic mutations in heterogeneous normal cells.

Single-cell genomics has advanced rapidly as trace-DNA amplification technologies evolved. However, current technologies are subject to a variety of pitfalls such as contamination, uneven genomic coverage, and amplification errors. Even for the "golden" strategy of single stem cell-derived clonal formation, high-fidelity amplification is applicable merely to single stem cells.

Author Correction: CRISPR interference-based specific and efficient gene inactivation in the brain.

In the version of this article initially published, the affiliation for Jian Zhang and Shuangli Mi was incomplete. In addition to the Key Laboratory of Genomics and Precision Medicine, they are also affiliated with the University of Chinese Academy of Sciences, Beijing, China. In Supplementary Fig.

CRISPR interference-based specific and efficient gene inactivation in the brain.

CRISPR-Cas9 has been demonstrated to delete genes in postmitotic neurons. Compared to the establishment of proliferative cell lines or animal strains, it is more challenging to acquire a highly homogeneous consequence of gene editing in a stable neural network. Here we show that dCas9-based CRISPR interference (CRISPRi) can efficiently silence genes in neurons.

Exosome and exosomal microRNA: trafficking, sorting, and function.

Exosomes are 40-100 nm nano-sized vesicles that are released from many cell types into the extracellular space. Such vesicles are widely distributed in various body fluids. Recently, mRNAs and microRNAs (miRNAs) have been identified in exosomes, which can be taken up by neighboring or distant cells and subsequently modulate recipient cells.

Identification of functional cooperative mutations of SETD2 in human acute leukemia.

Acute leukemia characterized by chromosomal rearrangements requires additional molecular disruptions to develop into full-blown malignancy, yet the cooperative mechanisms remain elusive. Using whole-genome sequencing of a pair of monozygotic twins discordant for MLL (also called KMT2A) gene-rearranged leukemia, we identified a transforming MLL-NRIP3 fusion gene and biallelic mutations in SETD2 (encoding a histone H3K36 methyltransferase). Moreover, loss-of-function point mutations in SETD2 were recurrent (6.

Circulating microRNAs as biomarkers for inflammatory diseases.

MicroRNAs (miRNAs), a class of small, non-coding RNA molecules with gene regulatory functions, have emerged to play a critical role in the pathogenesis of a variety of diseases. Current technological advances allow accurate, high throughput profiling of miRNA abundance in different tissues. More recently, extracellular, circulating miRNAs have begun to be demonstrated as highly stable, blood-based biomarkers for diseases.

An eQTL-based method identifies CTTN and ZMAT3 as pemetrexed susceptibility markers.

Pemetrexed, approved for the treatment of non-small cell lung cancer and malignant mesothelioma, has adverse effects including neutropenia, leucopenia, thrombocytopenia, anemia, fatigue and nausea. The results we report here represent the first genome-wide study aimed at identifying genetic predictors of pemetrexed response. We utilized expression quantitative trait loci (eQTLs) mapping combined with drug-induced cytotoxicity data to gain mechanistic insights into the observed genetic associations with pemetrexed susceptibility.

Rapid growth of a hepatocellular carcinoma and the driving mutations revealed by cell-population genetic analysis of whole-genome data.

We present the analysis of the evolution of tumors in a case of hepatocellular carcinoma. This case is particularly informative about cancer growth dynamics and the underlying driving mutations. We sampled nine different sections from three tumors and seven more sections from the adjacent nontumor tissues.

Platinum sensitivity-related germline polymorphism discovered via a cell-based approach and analysis of its association with outcome in ovarian cancer patients.

Purpose: Cell-based approaches were used to identify genetic markers predictive of patients' risk for poor response prior to chemotherapy.

Experimental Design: We conducted genome-wide association studies (GWAS) to identify single-nucleotide polymorphisms (SNP) associated with cellular sensitivity to carboplatin through their effects on mRNA expression using International HapMap lymphoblastoid cell lines (LCL) and replicated them in additional LCLs. SNPs passing both stages of the cell-based study were tested for association with progression-free survival (PFS) in patients.

MLL fusion proteins preferentially regulate a subset of wild-type MLL target genes in the leukemic genome.

MLL encodes a histone methyltransferase that is critical in maintaining gene expression during embryonic development and hematopoiesis. 11q23 translocations result in the formation of chimeric MLL fusion proteins that act as potent drivers of acute leukemia. However, it remains unclear what portion of the leukemic genome is under the direct control of MLL fusions.