ARID3C Acts as a Regulator of Monocyte-to-Macrophage Differentiation Interacting with NPM1.

ARID3C is a protein located on human chromosome 9 and expressed at low levels in various organs, yet its biological function has not been elucidated. In this study, we investigated both the cellular localization and function of ARID3C. Employing a combination of LC-MS/MS and deep learning techniques, we identified NPM1 as a binding partner for ARID3C's nuclear shuttling. ARID3C was found to predominantly localize with the nucleus, where it functioned as a transcription factor for genes STAT3, STAT1, and JUNB, thereby facilitating monocyte-to-macrophage differentiation. The precise binding sites between ARID3C and NPM1 were predicted by AlphaFold2. Mutating this binding site prevented ARID3C from interacting with NPM1, resulting in its retention in the cytoplasm instead of translocation to the nucleus. Consequently, ARID3C lost its ability to bind to the promoters of target genes, leading to a loss of monocyte-to-macrophage differentiation. Collectively, our findings indicate that ARID3C forms a complex with NPM1 to translocate to the nucleus, acting as a transcription factor that promotes the expression of the genes involved in monocyte-to-macrophage differentiation.

Exosome proteomes reveal glycolysis-related enzyme enrichment in primary canine mammary gland tumor compared to metastases.

OBJECTIVE: Numerous evidence has highlighted the differences between primary tumors and metastases. Nonetheless, the differences in exosomal proteins derived from primary tumor and metastases remain elusive. Here, we aimed to identify differentially expressed exosomal proteins from primary canine mammary gland tumor and metastases to understand how they shape their own tumor microenvironment. METHODS: We clearly distinguished primary canine mammary gland tumors (CHMp) from metastases (CHMm) and profiled the proteins within their secreted exosomes using LC-MS/MS. Moreover, the abundance of glycolysis enzymes (GPI, LDHA) in CHMp exosome was verified with Western blotting, To broaden the scope, we extended to human colorectal cancer-derived exosomes (SW480 vs. SW620) for comparison. RESULTS: We identified significant differences in 87 and 65 proteins derived from CHMp and CHMm, respectively. Notably, glycolysis enzymes (GPI, LDHA, LDHB, TPI1, and ALDOA) showed specific enrichment in exosomes from the primary tumor. CONCLUSION: We observed significant differences in the cellular proteome between primary tumors and metastases, and intriguingly, we identified a parallel heterogeneity the protein composition of exosomes. Specifically, we reported that glycolysis enzymes were significantly enriched in CHMp exosomes compared to CHMm exosomes. We further demonstrated that this quantitative difference in glycolysis enzymes persisted across primary and metastases, extending to human colorectal cancer-derived exosomes (SW480 vs. SW620). Our findings of the specific enrichment of glycolysis enzymes in primary tumor-derived exosomes contribute to a better understanding of tumor microenvironment modulation and heterogeneity between primary tumors and metastases.

Noncanonical immune response to the inhibition of DNA methylation by Staufen1 via stabilization of endogenous retrovirus RNAs.

DNA-methyltransferase inhibitors (DNMTis), such as azacitidine and decitabine, are used clinically to treat myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Decitabine activates the transcription of endogenous retroviruses (ERVs), which can induce immune response by acting as cellular double-stranded RNAs (dsRNAs). Yet, the posttranscriptional regulation of ERV dsRNAs remains uninvestigated. Here, we find that the viral mimicry and subsequent cell death in response to decitabine require the dsRNA-binding protein Staufen1 (Stau1). We show that Stau1 directly binds to ERV RNAs and stabilizes them in a genome-wide manner. Furthermore, Stau1-mediated stabilization requires a long noncoding RNA TINCR, which enhances the interaction between Stau1 and ERV RNAs. Analysis of a clinical patient cohort reveals that MDS and AML patients with lower Stau1 and TINCR expressions exhibit inferior treatment outcomes to DNMTi therapy. Overall, our study reveals the posttranscriptional regulatory mechanism of ERVs and identifies the Stau1-TINCR complex as a potential target for predicting the efficacy of DNMTis and other drugs that rely on dsRNAs.

The landscape of PBMC methylome in canine mammary tumors reveals the epigenetic regulation of immune marker genes and its potential application in predicting tumor malignancy.

BACKGROUND: Genome-wide dysregulation of CpG methylation accompanies tumor progression and characteristic states of cancer cells, prompting a rationale for biomarker development. Understanding how the archetypic epigenetic modification determines systemic contributions of immune cell types is the key to further clinical benefits. RESULTS: In this study, we characterized the differential DNA methylome landscapes of peripheral blood mononuclear cells (PBMCs) from 76 canines using methylated CpG-binding domain sequencing (MBD-seq). Through gene set enrichment analysis, we discovered that genes involved in the growth and differentiation of T- and B-cells are highly methylated in tumor PBMCs. We also revealed the increased methylation at single CpG resolution and reversed expression in representative marker genes regulating immune cell proliferation (BACH2, SH2D1A, TXK, UHRF1). Furthermore, we utilized the PBMC methylome to effectively differentiate between benign and malignant tumors and the presence of mammary gland tumors through a machine-learning approach. CONCLUSIONS: This research contributes to a better knowledge of the comprehensive epigenetic regulation of circulating immune cells responding to tumors and suggests a new framework for identifying benign and malignant cancers using genome-wide methylome.

ABCA9, an ER cholesterol transporter, inhibits breast cancer cell proliferation via SREBP-2 signaling.

The association between cholesterol metabolism and cancer development and progression has been recently highlighted. However, the role and function of many cholesterol transporters remain largely unknown. Here, we focused on the ATP-binding cassette subfamily A member 9 (ABCA9) transporter given that its expression is significantly downregulated in both canine mammary tumors and human breast cancers, which in breast cancer patients correlates with poor prognosis. We found that ABCA9 is mainly present in the endoplasmic reticulum (ER) and is responsible for promoting cholesterol accumulation in this structure. Accordingly, ABCA9 inhibited sterol-regulatory element binding protein-2 (SREBP-2) translocation from the ER to the nucleus, a crucial step for cholesterol synthesis, resulting in the downregulation of cholesterol synthesis gene expression. ABCA9 expression in breast cancer cells attenuated cell proliferation and reduced their colony-forming abilities. We identified ABCA9 expression to be regulated by Forkhead box O1 (FOXO1). Inhibition of PI3K induced enhanced ABCA9 expression through the activation of the PI3K-Akt-FOXO1 pathway in breast cancer cells. Altogether, our study suggests that ABCA9 functions as an ER cholesterol transporter that suppresses cholesterol synthesis via the inhibition of SREBP-2 signaling and that its restoration halts breast cancer cell proliferation. Our findings provide novel insight into the vital role of ABCA9 in breast cancer progression.

The role and medical prospects of long non-coding RNAs in cardiovascular disease.

Cardiovascular disease (CVD) has reached epidemic proportions and is a leading cause of death worldwide. One of the long-standing goals of scientists is to repair heart tissue damaged by various forms of CVD such as cardiac hypertrophy, dilated cardiomyopathy, myocardial infarction, heart fibrosis, and genetic and developmental heart defects such as heart valve deformities. Damaged or defective heart tissue has limited regenerative capacity and results in a loss of functioning myocardium. Advances in transcriptomic profiling technology have revealed that long noncoding RNA (lncRNA) is transcribed from what was once considered "junk DNA." It has since been discovered that lncRNAs play a critical role in the pathogenesis of various CVDs and in myocardial regeneration. This review will explore how lncRNAs impact various forms of CVD as well as those involved in cardiomyocyte regeneration. Further, we discuss the potential of lncRNAs as a therapeutic modality for treating CVD.

Asia-Oceania HUPO: Past, Present, and Future.

The Asia-Oceania Human Proteome Organization (AOHUPO; www.aohupo.org) was officially founded on June 7, 2001, by Richard J. Simpson (Australia), Akira Tsugita (Japan), and Young-Ki Paik (Korea) and launched on October 1-4, 2001, at the second scientific meeting of the International Proteomics Conference held in Canberra, Australia. Inaugural council members of the AOHUPO elected were Richard J. Simpson (Australia, president), Qi-Chang Xia (China), Kazuyuki Nakamura (Japan), Akira Tsugita (Japan, VIce President), Young-Ki Paik (Korea, secretary general), Mike Hubbard (New Zealand), Max C. M. Chung (Singapore), Shui-Tien Chen (Taiwan), and John Bennett (Philippines). The first AOHUPO conference was held on March 26-27, 2002, at the Seoul National University, Seoul, Korea, conjointly with the second Annual Meeting of KHUPO. Since then, biennial AOHUPO conferences have been held in Taipei (2004), Singapore (2006), Cairns (2008), Hyderabad (2010), Beijing (2012), Bangkok (2014), Sun Moon Lake (2016), and Osaka (2018). The 10th AOHUPO conference is scheduled to be held in Busan on June 30 to July 2, 2021, to celebrate our 20th anniversary.

CXCL5 secreted from macrophages during cold exposure mediates white adipose tissue browning.

Adipose tissue affects metabolic-related diseases because it consists of various cell types involved in fat metabolism and adipokine release. CXC ligand 5 (CXCL5) is a member of the CXC chemokine family and is highly expressed by macrophages in white adipose tissue (WAT). In this study, we generated and investigated the function of CXCL5 in knockout (KO) mice using CRISPR/Cas9. The male KO mice did not show significant phenotype differences in normal conditions. However, proteomic analysis revealed that many proteins involved in fatty acid beta-oxidation and mitochondrial localization were enriched in the inguinal WAT (iWAT) of Cxcl5 KO mice. Cxcl5 KO mice also showed decreased protein and transcript expression of genes associated with thermogenesis, including uncoupling protein 1 (UCP1), a well-known thermogenic gene, and increased expression of genes associated with inflammation. The increase in UCP1 expression in cold conditions was significantly retarded in Cxcl5 KO mice. Finally, we found that CXCL5 treatment increased the expression of transcription factors that mediate Ucp1 expression and Ucp1 itself. Collectively, our data show that Ucp1 expression is induced in adipocytes by CXCL5, which is secreted upon ß-adrenergic stimulation by cold stimulation in M1 macrophages. Our data indicate that CXCL5 plays a crucial role in regulating energy metabolism, particularly upon cold exposure. These results strongly suggest that targeting CXCL5 could be a potential therapeutic strategy for people suffering from disorders affecting energy metabolism.

Spatiotemporal expression of long noncoding RNA Moshe modulates heart cell lineage commitment.

The roles of long non-coding RNA (LncRNA) have been highlighted in various development processes including congenital heart defects (CHD). Here, we characterized the molecular function of LncRNA, Moshe (1010001N08ik-203), one of the Gata6 antisense transcripts located upstream of Gata6, which is involved in both heart development and the most common type of congenital heart defect, atrial septal defect (ASD). During mouse embryonic development, Moshe was first detected during the cardiac mesoderm stage (E8.5 to E9.5) where Gata6 is expressed and continues to increase at the atrioventricular septum (E12.5), which is involved in ASD. Functionally, the knock-down of Moshe during cardiogenesis caused significant repression of Nkx2.5 in cardiac progenitor stages and resulted in the increase in major SHF lineage genes, such as cardiac transcriptional factors (Isl1, Hand2, Tbx2), endothelial-specific genes (Cd31, Flk1, Tie1, vWF), a smooth muscle actin (a-Sma) and sinoatrial node-specific genes (Shox2, Tbx18). Chromatin Isolation by RNA Purification showed Moshe activates Nkx2.5 gene expression via direct binding to its promoter region. Of note, Moshe was conserved across species, including human, pig and mouse. Altogether, this study suggests that Moshe is a heart-enriched lncRNA that controls a sophisticated network of cardiogenesis by repressing genes in SHF via Nkx2.5 during cardiac development and may play an important role in ASD.

Proteomic analysis of aqueous humor in canine primary angle-closure glaucoma in American Cocker Spaniel dogs.

OBJECTIVE: To analyze proteomic profiles of the aqueous humor (AH) of canines with primary angle-closure glaucoma (PACG) and identify associated protein alterations. ANIMALS STUDIED: Six American Cocker Spaniels with PACG and six American Cocker Spaniels without ocular diseases. METHODS: Aqueous humor samples were collected from six American Cocker Spaniels with PACG at Seoul National University, VMTH, and six healthy Cocker Spaniels without ocular disease at Irion Animal Hospital. For the PACG group, AH samples were obtained by anterior chamber paracentesis prior to glaucoma treatment. For the AH control group, AH samples were collected from patients anesthetized for other reasons. Total AH protein concentration was determined by the bicinchoninic acid (BCA) assay. AH protein samples were quantified by liquid chromatography-mass spectrometry (LC-MS/MS). Raw MS spectra were processed using MaxQuant software 30, and the Gene Ontology (GO) enrichment analysis was performed using ClueGO. RESULTS: The AH protein concentration in the PACG group (10.49 ± 17.98 µg/µl) was significantly higher than that of the control group (0.45 ± 0.11 µg/µl; p < .05). A total of 758 proteins were identified in the AH. Several proteins both significantly increased (n = 69) and decreased (n = 252) in the PACG group compared to those in the control group. GO enrichment analysis showed that the "response to wounding," "negative regulation of endopeptidase activity," and "cell growth" pathways were the most enriched terms in the PACG group compared to the control group. The top 5 proteins that were significantly increased in the AH of the PACG group were secreted phosphoprotein 1 (SPP1), peptidoglycan recognition proteins 2 (PGLYRP2), tyrosine 3-monooxygenase (YWHAE), maltase-glucoamylase (MGAM), and vimentin (VIM). CONCLUSIONS: Gene Ontology enrichment analysis using the proteomic data showed that proteins and pathways related to inflammation were significantly upregulated in the various stage of PACG. Proteomic analysis of the AH from the PACG may provide valuable insights into PACG pathogenesis.

METTL8 mRNA Methyltransferase Enhances Cancer Cell Migration via Direct Binding to ARID1A.

The association of RNA modification in cancer has recently been highlighted. Methyltransferase like 8 (METTL8) is an enzyme and its role in mRNA m3C modification has barely been studied. In this study, we found that METTL8 expression was significantly up-regulated in canine mammary tumor and investigated its functional roles in the tumor process, including cancer cell proliferation and migration. METTL8 expression was up-regulated in most human breast cancer cell lines tested and decreased by Yin Yang 1 (YY1) transcription factor knockdown, suggesting that YY1 is a regulating transcription factor. The knockdown of METTL8 attenuated tumor cell growth and strongly blocked tumor cell migration. AT-rich interactive domain-containing protein 1A (ARID1A) was identified as a candidate mRNA by METTL8. ARID1A mRNA binds to METTL8 protein. ARID1A mRNA expression was not changed by METTL8 knockdown, but ARID1A protein level was significantly increased. Collectively, our study indicates that METTL8 up-regulated by YY1 in breast cancer plays an important role in cancer cell migration through the mRNA modification of ARID1A, resulting in the attenuation of its translation.

CD276 (B7-H3) Maintains Proliferation and Regulates Differentiation in Angiogenic Function in Late Endothelial Progenitor Cells.

Endothelial progenitor cells (EPCs) provide an important source of recovery from blood vessel dysfunction. Late EPCs (LEPCs) are circulating blood cells that are capable of promoting vascular repair. Using transcriptome analysis, we identified distinctive LEPC profiles and found that CD276 (B7-H3) mRNA is strongly expressed in LEPCs. CD276 protein is present abundantly on the cell surface of LEPC when analyzed by fluorescence-activated cell sorter and immunocytochemistry. CD276, a B7 family member, is a type I transmembrane glycoprotein. The role of CD276 in LEPCs remains unknown. CD276 knockdown by lentivirus transduction in LEPCs significantly decreased proliferation and increased apoptosis of LEPCs in vitro. After CD276 silencing, the cell cycle of LEPCs was prone to remain at the G0/G1 phase, and the cell migration rates as well as transwell and wound-healing migration were decreased. CD276 knockdown in LEPCs increased the G1 phase regulators cyclin D2/D3/E1-cyclin-dependent kinases (CDK2/4/6), but decreased the S-G2-M phase regulators cyclin A/B-CDK1. However, LEPCs with CD276 knockdown resulted in increased tube formation in vitro and angiogenesis in a Matrigel plug assay in vivo. FoxC1/C2, an upstream signal of Notch in arterial cell proliferation, and Hey1/2, which is known to promote arterial differentiation in the vasculature, were upregulated in CD276 knockdown LEPCs. In LEPCS, CD276 has a positive effect on proliferation and migration of endothelial cells, but negative effects on angiogenesis, particularly endothelial cell differentiation. Our data indicate, for therapeutic purpose, that CD276 can be used to acquire and maintain cell populations of LEPCs and blocking CD276 will promote angiogenetic differentiation. We found that CD276 (B7-H3) is enriched on the cell membrane of LEPCs. CD276 knockdown reduced proliferation and migration of LEPCs by increasing cell cycle inhibitors such as p21cip1 and pRb and decreasing pErk1/2 and pAkt but promoted angiogenesis and endothelial cell differentiation by elevating vascular endothelial growth factor-vascular endothelial growth factor receptor 1 and p-p38. Stem Cells 2019;37:382-394.

Neural precursor cell-expressed, developmentally down-regulated 4 (NEDD4) regulates hydrogen peroxide-induced cell proliferation and death through inhibition of Hippo signaling.

E3 ubiquitin ligases are involved in the regulation of oxidative stress-induced cell death. In this study, we investigated the role of neural precursor cell-expressed, developmentally down-regulated protein 4 (NEDD4) in regulation of hydrogen peroxide (H2O2)-induced cell proliferation and apoptosis in human bone marrow-derived stem cells (hBMSCs). Cell proliferation was increased in low doses of H2O2 (10-4 to 10-2 µM), whereas sublethal concentrations of H2O2 (>200 µM) induced apoptosis. A chromatin immunoprecipitation assay identified that recruitment of NF-κB onto the promoter region of NEDD4 mediated H2O2-induced NEDD4 expression. The increase of NEDD4 expression by H2O2 induced translocation of yes-associated protein (YAP) into the nucleus by decreasing the stability of large tumor suppressor kinase (LATS). Thus, the phosphorylation of serine 127 residue of YAP by LATS upstream kinase is decreased and thereby increased the transcriptional activity of YAP. The mRNA expression levels of catalase and manganese superoxide dismutase, which are well-known targets of YAP, were increased by H2O2 treatment but down-regulated by NEDD4 silencing using a specific small interfering RNA targeting NEDD4 (siNEDD4). H2O2-induced scavenging capacity of reactive oxygen species was also decreased by siNEDD4 in hBMSCs. Finally, hBMSC differentiation into osteoblast was decreased by siNEDD4 but reverted by reintroduction of the S127A mutant construction of YAP. Taken together, these results indicate that NEDD4 regulates H2O2-induced alteration of cell status through regulation of the Hippo signaling pathway.-Jeon, S.-A., Kim, D. W., Cho, J.-Y. Neural precursor cell-expressed, developmentally down-regulated 4 (NEDD4) regulates hydrogen peroxide-induced cell proliferation and death through inhibition of Hippo signaling.

Role of growth factors in hematopoietic stem cell niche.

Hematopoietic stem cells (HSCs) produce new blood cells everyday throughout life, which is maintained by the self-renewal and differentiation ability of HSCs. This is not controlled by the HSCs alone, but rather by the complex and exquisite microenvironment surrounding the HSCs, which is called the bone marrow niche and consists of various bone marrow cells, growth factors, and cytokines. It is essential to understand the characteristic role of the stem cell niche and the growth factors in the niche formation. In this review, we describe the role of the bone marrow niche and factors for niche homeostasis, and also summarize the latest research related to stem cell niche.

Long Non-Coding RNA Associated with Cholesterol Homeostasis and Its Involvement in Metabolic Diseases.

Cholesterol is an essential cell component that functions to create and maintain all kinds of cell membranes and lipoprotein particles. It is crucial to maintain the proper amount of cholesterol at both the cellular and systemic level. Recently, the importance of cholesterol has been reported not only in various cell development processes but also in the development of diseases. Furthermore, the involvement of long non-coding RNAs (lncRNAs), which are regarded as important epigenetic regulators in gene expression, has also been reported in cholesterol homeostasis. It is thus necessary to summarize the research on lncRNAs related to cholesterol with increased interest. This review organized the role of lncRNAs according to the major issues in cholesterol homeostasis: efflux, metabolism and synthesis, and disease process.

ANK2 Hypermethylation in Canine Mammary Tumors and Human Breast Cancer.

Canine mammary tumors (CMT) constitute the most common tumor types found in female dogs. Understanding this cancer through extensive research is important not only for clinical veterinary applications, but also in the scope of comparative oncology. The use of DNA methylation as a biomarker has been noted for numerous cancers in the form of both tissue and liquid biopsies, yet the study of methylation in CMT has been limited. By analyzing our canine methyl-binding domain sequencing (MBD-seq) data, we identified intron regions of canine ANK2 and EPAS1 as differentially methylated regions (DMGs) in CMT. Subsequently, we established quantitative methylation specific PCR (qMSP) of ANK2 and EPAS1 to validate the target hypermethylation in CMT tissue, as well as cell free DNA (cfDNA) from CMT plasma. Both ANK2 and EPAS1 were hypermethylated in CMT and highlighted as potential tissue biomarkers in CMT. ANK2 additionally showed significant hypermethylation in the plasma cfDNA of CMT, indicating that it could be a potential liquid biopsy biomarker as well. A similar trend towards hypermethylation was indicated in HBC at a specific CpG of the ANK2 target on the orthologous human region, which validates the comparative approach using aberrant methylation in CMT.

Common Repository of FBS Proteins (cRFP) To Be Added to a Search Database for Mass Spectrometric Analysis of Cell Secretome.

We propose to use cRFP (common Repository of FBS Proteins) in the MS (mass spectrometry) raw data search of cell secretomes. cRFP is a small supplementary sequence list of highly abundant fetal bovine serum proteins added to the reference database in use. The aim behind using cRFP is to prevent the contaminant FBS proteins from being misidentified as other proteins in the reference database, just as we would use cRAP (common Repository of Adventitious Proteins) to prevent contaminant proteins present either by accident or through unavoidable contacts from being misidentified as other proteins. We expect it to be widely used in experiments where the proteins are obtained from serum-free media after thorough washing of the cells, or from a complex media such as SILAC, or from extracellular vesicles directly.

Transposable element-mediated structural variation analysis in dog breeds using whole-genome sequencing.

Naturally occurring diseases in dogs provide an important animal model for studying human disease including cancer, heart disease, and autoimmune disorders. Transposable elements (TEs) make up ~ 31% of the dog (Canis lupus familiaris) genome and are one of main drivers to cause genomic variations and alter gene expression patterns of the host genes, which could result in genetic diseases. To detect structural variations (SVs), we conducted whole-genome sequencing of three different breeds, including Maltese, Poodle, and Yorkshire Terrier. Genomic SVs were detected and visualized using BreakDancer program. We identified a total of 2328 deletion SV events in the three breeds compared with the dog reference genome of Boxer. The majority of the genetic variants were found to be TE insertion polymorphism (1229) and the others were TE-mediated deletion (489), non-TE-mediated deletion (542), simple repeat-mediated deletion (32), and other indel (36). Among the TE insertion polymorphism, 286 elements were full-length LINE-1s (L1s). In addition, the 49 SV candidates located in the genic regions were experimentally verified and their polymorphic rates within each breed were examined using PCR assay. Polymorphism analysis of the genomic variants revealed that some of the variants exist polymorphic in the three dog breeds, suggesting that their SV events recently occurred in the dog genome. The findings suggest that TEs have contributed to the genomic variations among the three dog breeds of Maltese, Poodle, and Yorkshire Terrier. In addition, the polymorphic events between the dog breeds indicate that TEs were recently retrotransposed in the dog genome.

Exploring the key communicator role of exosomes in cancer microenvironment through proteomics.

There have been many attempts to fully understand the mechanism of cancer behavior. Yet, how cancers develop and metastasize still remain elusive. Emerging concepts of cancer biology in recent years have focused on the communication of cancer with its microenvironment, since cancer cannot grow and live alone. Cancer needs to communicate with other cells for survival, and thus they secrete various messengers, including exosomes that contain many proteins, miRNAs, mRNAs, etc., for construction of the tumor microenvironment. Moreover, these intercellular communications between cancer and its microenvironment, including stromal cells or distant cells, can promote tumor growth, metastasis, and escape from immune surveillance. In this review, we summarized the role of proteins in the exosome as communicators between cancer and its microenvironment. Consequently, we present cancer specific exosome proteins and their unique roles in the interaction between cancer and its microenvironment. Clinically, these exosomes might provide useful biomarkers for cancer diagnosis and therapeutic tools for cancer treatment.

Concise approach for screening long non-coding RNAs functionally linked to human breast cancer associated genes.

Cancer research studies using next-generation sequencing have revealed a number of genes of which aberrant expression is associated with various cancers. Recently, long non-coding RNA (lncRNA) has been highlighted due to its tissue-specific expression and cell cancerization functions, such as the regulation of key tumor suppressors. In this study, we suggest a very efficient approach to survey lncRNAs putatively associated with breast cancer. We targeted lncRNAs linked with breast cancer associated genes (BCAGs) and analyzed their expression pattern in human breast cancer cell lines. A total of 337 BCAGs were retrieved from literature review and the existence of 121 lncRNAs were identified from the 15 kb up- and downstream regions of the list of genes. Twenty lncRNAs' expression were detectable in human breast cancer cell lines with different expression patterns. Interestingly, the expression of three lncRNAs, two up-regulated (RAD51C v.4, LOC105371849) and one down-regulated (LOC102724064), were closely correlated with adjacent BCAGs (RAD51C, HEATR6 and BRMS1) in breast cancer cell lines. We thus demonstrated association between the lncRNA and its adjacent BCAG using LOC105371849-HEATR6, of which the function and regulation in breast cancer are still unknown. Knockdown of LOC105371849 by siRNA decreased the expression of HEATR6 mRNA in the MCF7 human breast cancer cell line. In conclusion, this study provides a better understanding about the biological roles of lncRNAs in breast cancer and may be useful in the investigation of proper targets for diagnostic and/or therapeutic breast cancer markers using public databases.