- RNA Research and Splicing
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- RNA and protein synthesis mechanisms
- Wnt/β-catenin signaling in development and cancer
- Cancer Cells and Metastasis
- DNA Repair Mechanisms
- Microtubule and mitosis dynamics
- BRCA gene mutations in cancer
- Protease and Inhibitor Mechanisms
- Cell Adhesion Molecules Research
- Peptidase Inhibition and Analysis
- RNA regulation and disease
- Cancer-related gene regulation
- RNA Interference and Gene Delivery
- Cancer Genomics and Diagnostics
- Kruppel-like factors research
- Click Chemistry and Applications
- Renal and related cancers
- Immunotherapy and Immune Responses
- Mitochondrial Function and Pathology
- Cellular transport and secretion
- Nutrition, Genetics, and Disease
- Cellular Mechanics and Interactions
- Bone and Dental Protein Studies
Dalian Medical University
2015-2023
John Wiley & Sons (United States)
2016
Second Affiliated Hospital of Dalian Medical University
2016
Dalian University
2015
Harvard University
2007-2012
German Cancer Research Center
2006-2008
Heidelberg University
2006-2008
University of Southampton
2003-2006
Karolinska Institutet
2001-2005
Zero to Three
2002
Integrins control the cell attachment to extracellular matrix and play an important role in mediating proliferation, migration survival. A number of cancer-associated integrin genes can be regulated by microRNAs (miRNAs) that bind their target sites 3′ untranslated regions. We examined effect single-nucleotide polymorphisms (SNPs) predicted miRNA six ( ITGA3 , ITGA6 ITGAv ITGB3 ITGB4 ITGB5 ) on breast cancer (BC) risk clinical outcome. Six SNPs were genotyped 749 Swedish incident BC cases...
ErbB2 overexpression identifies a subset of breast cancer as ErbB2-positive and is frequently associated with poor clinical outcomes. As membrane-embedded receptor tyrosine kinase, cell surface levels are regulated dynamically by membrane physical properties. The present study aims to investigate the influence cholesterol contents on status cellular responses its kinase inhibitors. abundance was examined in cells using filipin staining. Cellular localizations were investigated...
A great deal is known about the export of spliced mRNAs, but little mRNAs encoded by human cellular genes that naturally lack introns. Here, we investigated requirements for three intronless (HSPB3, IFN-α1, and IFN-β1). Significantly, found all are stable accumulate in cytoplasm, whereas size-matched random RNAs unstable detected only nucleus. portion coding region confers this stability cytoplasmic localization on a cDNA transcript, which normally retained nucleus degraded. polyadenylation...
We previously showed that mRNAs synthesized from three genes naturally lack introns contain a portion of their coding sequence, known as cytoplasmic accumulation region (CAR), which is essential for stable the intronless in cytoplasm. The CAR each mRNA unexpectedly large, ranging size ∼160 to 285 nt. Here, we identified one or more copies 10-nt consensus sequence CAR. To determine whether this element (designated CAR-E) functions mRNA, multimerized most conserved CAR-E and inserted it...
In contrast to cytoplasmic localization of spliced mRNAs, many lncRNAs are localized in the nucleus. To investigate mechanism, we used lncRNA MEG3 as a reporter and mapped potent nuclear retention element (NRE), deletion this led striking export from nucleus cytoplasm. Insertion NRE resulted well mRNA. We further purified RNP assembled on vitro identified proteins by mass spectrometry. Screen using siRNA revealed depletion U1 snRNP components SNRPA, SNRNP70 or SNRPD2 caused significant...
Abstract Mutations and diminished expression of the E‐cadherin gene (CDH1) have been identified in a number epithelial malignancies. Although somatic CDH1 mutations were detected lobular breast cancer with frequency ranging from 10–56%, alterations more frequent ductal tumors appear to be rare. Here we analyzed coding region for using denaturing high performance liquid chromatography found 4 83 carcinomas (5%) 3 25 (12%). The germline 13 patients familial was also mutations, but none...
Xeroderma pigmentosum group A (XPA)-binding protein 2 (XAB2) is a multi-functional that plays critical role in processes including transcription, transcription-coupled DNA repair, pre-mRNA splicing, homologous recombination and mRNA export. Microarray analysis on gene expression XAB2 knockdown cells reveals many genes with significant change function mitotic cell cycle regulation. Fluorescence-activated scanner confirmed depletion led to arrest G2/M phase, mostly at prophase or prometaphase....
A great deal of progress in understanding gene expression has been made using vitro systems. For most studies, functional assays are carried out extracts that prepared bulk from 10-50 or more liters cells grown suspension. However, these large-scale preparations not amenable to rapidly testing effects result a variety vivo cellular treatments conditions. This journal video article shows method for preparing small-scale nuclear extracts, HeLa as an example. is few three 150 mm plates adherent...
The TREX-TAP pathway is vital for mRNA export. For spliced mRNA, the TREX complex recruited during splicing; however, intronless recruitment sequence dependent. However, export of cytoplasmic long noncoding RNA (lncRNA) poorly characterized. We report identification a accumulation region (CAR-N) in lncRNA, NKILA. CAR-N removal led to strong nuclear retention NKILA, and insertion promoted cDNA transcripts. In vitro RNP purification via CAR-N, mass spectrometry, siRNA screening revealed that...
Tumor metastasis remains the main cause of breast cancer-related deaths, especially delayed cancer distant metastasis. The current study assessed frequency CD44 - /CD24 cells in 576 tissue specimens for associations with clinicopathological features and investigated underlying molecular mechanisms. results indicated that higher (≥19.5%) was associated postoperative Furthermore, triple negative (TNBC) spontaneously converted into + stem (CSCs) properties similar to CSCs from primary human...
The branch point sequence (BPS) is a conserved splicing signal important for spliceosome assembly and lariat intron formation. BPS mutations may result in aberrant pre-mRNA genetic disorders, but their phenotypic consequences have been difficult to predict, largely due highly degenerate nature of the consensus. Here, we examined pattern nine reporter pre-mRNAs that previously shown give rise human hereditary diseases as single-nucleotide substitutions predicted BPS. Increased exon skipping...
In order to explore the possible role of E-cadherin in familial cancer, 19 breast cancer patients, whose tumours demonstrated loss heterozygosity (LOH) at locus, were screened for germline mutations. No pathogenic alterations detected these individuals. However, a somatic mutation was found (49-2A→C) one tumours. This tumour showed pattern both ductal and lobular histology. Another 10 families with cases breast, gastric colon also mutations, no mutations found. A missense exon 12 (1774G→A;...
Auxiliary splicing signals in introns play an important role splice site selection, but these elements are poorly understood. We show that a subset of serine/arginine (SR)-rich proteins activate cryptic 3′ sense Alu repeat located intron 4 the human LST1 gene. Utilization this is controlled by juxtaposed Alu-derived silencers and enhancers between closely linked short tandem repeats TNFd TNFe. Systematic mutagenesis showed AG dinucleotides were not preceded purine residues critical for...
// Hao Zhang 1, * , Minna Luo 2, Zining Jin 3, Dan Wang 1 Ming Sun 4 Xinhan Zhao 2 Zuowei Haixin Lei 5 Man Li Caigang Liu Breast Disease and Reconstruction Center, Cancer Key Lab of Dalian, The Second Hospital Dalian Medical University, China Department Oncology, First Affiliated Hospital, Xi'an Jiaotong Xi'an, 3 surgery, Shenyang, Shengjing Institute Stem Cell, These authors have contributed equally to this work Correspondence to: Li, e-mail: limanrn007@163.com Lei, haixinlei@dlmedu.edu.cn...
Abstract XAB2 is a multi-functional protein participating processes including transcription, splicing, DNA repair and mRNA export. Here, we report POLR2A, the largest catalytic subunit of RNA polymerase II, as major target gene down-regulated after depletion. depletion led to severe splicing defects POLR2A with significant intron retention. Such resulted in substantial loss at levels, which further impaired global transcription. Treatment inhibitor madrasin induced similar reduction POLR2A....
A great deal of progress in understanding gene expression has been made using vitro systems. For most studies, functional assays are carried out extracts that prepared bulk from 10-50 or more liters cells grown suspension. However, these large-scale preparations not amenable to rapidly testing effects result a variety vivo cellular treatments conditions. This journal video article shows method for preparing small-scale nuclear extracts, HeLa as an example. is few three 150 mm plates adherent...