Biomedical subjects

Heui-Soo Kim

Publications and source records attributed to Heui-Soo Kim.

At least 19 recordsLinked to original sources

PubMed2026

Tumor Suppressive Role of Hsa-miR-328-3p in Colon Cancer by Regulating EN2.

BACKGROUND/AIM: Colon cancer is a prevalent and life-threatening malignancy worldwide. Recent studies have focused on how microRNAs (miRNAs) act as post-transcriptional modulators in colon cancer progression. Herein, this study aimed to identify the impact of miRNAs that are decreased in colon cancer and to investigate their regulatory mechanisms. MATERIALS AND METHODS: Differentially expressed miRNAs (DEmiRNAs) and genes (DEGs) were identified through analysis of miRNA sequencing and RNA sequencing data from normal and tumor tissues in The Cancer Genome Atlas (TCGA). Expression levels were validated by quantitative polymerase chain reaction (qPCR) in both tissues and cell lines. Functional effects of miRNAs were evaluated by assessing cell viability, proliferation, migration, and invasion following transfection with miRNA mimics. RESULTS: Analysis of miRNA-seq data from the TCGA database identified hsa-miR-328-3p as a miRNA consistently downregulated across all stages of colon cancer. This downregulation was independently validated in colon cancer patient tissues by qPCR. Functional assays demonstrated that enforced expression of hsa-miR-328-3p significantly reduced cell viability, proliferation, migration, and invasion in colon cancer cell lines, supporting its tumor-suppressive role. To elucidate the molecular mechanism underlying these inhibitory effects, target gene analysis was performed. Engrailed homeobox 2 (EN2) was identified as a potential target of hsa-miR-328-3p, and a dual-luciferase assay confirmed that EN2 is directly regulated by hsa-miR-328-3p. CONCLUSION: Collectively, these findings indicate that hsa-miR-328-3p is frequently downregulated in colon cancer and functions as a tumor suppressor by negatively regulating its target gene, EN2, thereby contributing to colon cancer malignancy. EN2 may serve as a potential diagnostic biomarker for colon cancer, while restoration of hsa-miR-328-3p expression represents a promising therapeutic strategy. Further studies are needed to clarify the precise molecular mechanisms linking the hsa-miR-328-3p/EN2 axis to colon cancer progression.

Humans↗

PubMed2006

Formation of a new solo-LTR of the human endogenous retrovirus H family in human chromosome 21.

Human endogenous retroviruses (HERVs) contribute to various kinds of genomic instability via rearrangement and retrotransposition events. In the present study the formation of a new human-specific solo-LTR belonging to the HERV-H family (AP001667; chromosome 21q21) was detected by a comparative analysis of human chromosome 21 and chimpanzee chromosome 22. The solo-LTR was formed as a result of an equal homologous recombination excision event. Several evolutionary processes have occurred at this locus during primate evolution, indicating that mammalian-wide interspersed repeat (MIR) and full-length HERV-H elements integrated into hominoid genomes after the divergence of Old World monkeys and hominoids, and that the solo-LTR element was created by recombination excision of the HERV-H only in the human genome.

Animals↗

PubMed2006

Molecular genetic analyses of human endogenous retroviral elements belonging to the HERV-P family in primates, human tissues, and cancer cells.

Human endogenous retroviral sequences family P (HERV-P) proviral sequences have been located within the human genome. Here, we identify and analyze novel putative structural genes of HERV-P in primates, human tissues, and cancer cells with an aim toward better understanding their evolutionary relationships and transcriptional potential. The expression pattern of HERV-P structural genes indicates that they are actively amplified in human tissues and widely expressed in cancer cells, suggesting a potential role in carcinogenesis. Phylogenetic analyses suggest that the HERV-P family may be divided into two distinct categories that arose during primate evolution via active gene duplication. Taken together, our data provide a better understanding of the dynamic evolutionary features and potential functional roles of the HERV-P gene family.

Animals↗

PubMed2006

Phospholipase D1 is up-regulated in the mitochondrial fraction from the brains of Alzheimer's disease patients.

Mitochondrial dysfunction may play an important role in sporadic Alzheimer's disease (AD) progression. Recently, we have reported that amyloid precursor protein (APP) stimulates phospholipase D (PLD) activity and beta-amyloid (Abeta) region of APP is involved in the interaction with PLD1. To elucidate the involvement of PLD in the pathophysiology of AD, we examined the expression of PLD1 and alteration of membrane phospholipid in mitochondrial membranes of control and AD brains using Western blot and phospholipid analysis by thin layer chromatography (TLC). We have found that protein expression of PLD1 was significantly increased in mitochondrial fraction of brains of AD patients compared with that in control brains. Furthermore, the concentration of mitochondrial phospholipids such as phosphatidylcholine (PC) and phosphatidylethanolamine (PE) was increased and the content of phosphatidic acid (PA), a product of PLD activity, was up-regulated in the mitochondrial membrane fractions of AD brain compared with that of control brain. These results suggest that up-regulation of PLD1 in the mitochondrial fraction of AD brain might affect the composition of membrane phospholipids and provide a clue to the mechanism underlying the mitochondrial dysfunction associated with AD.

Aged↗

PubMed2006

LINE FUSION GENES: a database of LINE expression in human genes.

BACKGROUND: Long Interspersed Nuclear Elements (LINEs) are the most abundant retrotransposons in humans. About 79% of human genes are estimated to contain at least one segment of LINE per transcription unit. Recent studies have shown that LINE elements can affect protein sequences, splicing patterns and expression of human genes. DESCRIPTION: We have developed a database, LINE FUSION GENES, for elucidating LINE expression throughout the human gene database. We searched the 28,171 genes listed in the NCBI database for LINE elements and analyzed their structures and expression patterns. The results show that the mRNA sequences of 1,329 genes were affected by LINE expression. The LINE expression types were classified on the basis of LINEs in the 5' UTR, exon or 3' UTR sequences of the mRNAs. Our database provides further information, such as the tissue distribution and chromosomal location of the genes, and the domain structure that is changed by LINE integration. We have linked all the accession numbers to the NCBI data bank to provide mRNA sequences for subsequent users. CONCLUSION: We believe that our work will interest genome scientists and might help them to gain insight into the implications of LINE expression for human evolution and disease. AVAILABILITY: http://www.primate.or.kr/line.

Chromosome Mapping↗

PubMed2006

Molecular evolution of the periphilin gene in relation to human endogenous retrovirus m element.

HERV-M (human endogenous retrovirus M), related to the super family of HERV-K, has a methionine (M) tRNA primer-binding site, and is located within the periphilin gene on human chromosome 12q12. HERV-M has been integrated into the periphilin gene as the truncated form, 5'LTR-gag-pol-3'LTR. Polymerase chain reaction (PCR) and reverse transcription-polymerase chain reaction (RT-PCR) approaches were conducted to investigate its evolutionary origins. Interestingly, the insertion of retroelements in a common ancestor genome can make different transcript variants in different species. In the case of the periphilin gene, human (10 variants) and mouse (2 variants) lineages show different transcript variants. Insertion of HERV-M (variant 1-3) could affect the protein-coding region. Also, Alusq/x (variant 4-9) and L1ME4a (mammalian-wide subfamilies of LINE-1) (variant 10) in humans and SINE (short interspersed repetitive element) and RLTR15 (the mouse putative long terminal repeat) (variant 2) in mice could be driving forces in transcript diversification of the periphilin gene during mammalian evolution. The HERV-M derived transcripts (variant 1-3) were expressed in different human tissues, whereas they were not detected in crab-eating monkey and squirrel monkey tissues by RT-PCR amplification. Taken together, HERV-M seems to have been integrated into our common ancestor genome after the divergence of simians and prosimians, and then was actively expressed during hominoid evolution.

Alternative Splicing↗

PubMed2006

Human Endogenous Retrovirus (HERV)-R family in primates: Chromosomal location, gene expression, and evolution.

Hitherto, full-length endogenous retrovirus (HERV)-R has been located at human chromosome 7q11.2, and mRNA and envelope proteins have been detected in placenta and a variety of other cell types. In the present study, using a probe derived from the gorilla fosmid library, we detected the paralogous locus (7q31.3) of the HERV-R env gene in human chromosome 7q11.2, and also determined the chromosomal location in apes and Old World monkeys. The HERV-R gene was not detected in New World monkeys or prosimians with FISH and PCR analyses. We determined the sequences of the HERV-R env genes obtained from the genomic DNA of primates using PCR and sequencing tools. Except for a HERV-R env sequence derived from gorilla DNA, the functional domains of putative envelope proteins are conserved, suggesting that those domains could have a functional capacity in the primate genome. In addition, we investigated the env gene expression of HERV-R in various human tissues and cancer cells. An RT-PCR approach indicated that the env gene was expressed in several human tissues (brain, prostate, testis, kidney, placenta, thymus, and uterus) and cancer cells (RT4, BT-474, MCF7, OVCAR-3, LOX-IMVI, and AZ521). Taken together, our data could be of great use for understanding the evolutionary dynamics of HERV-R through primate radiation as well as the implications of its functional role in human tissues and cancers cells.

Animals↗

PubMed2006

Human endogenous retrovirus HERV-H family in human tissues and cancer cells: expression, identification, and phylogeny.

HERV-H family is the most abundant HERV families in the human genome with more than 1000 copies including full-length, truncated form, and solitary LTRs. We investigated envelope (env) gene fragments of HERV-H family in various human tissues and cancer cells. The env fragments were detected in mRNA of several human tissues (placenta, skeletal muscle, spleen, and thymus) and cancer cells (RT4, BT-474, HCT-116, TE-1, UO-31, Jurkat, HepG2, A549, MCF7, OVCAR-3, MIA-PaCa-2, PC3, LOX-IMVI, AZ521, 2F7, U-937, and C-33A) by RT-PCR approach. The RT-PCR products were cloned and sequenced. New 12 clones from human tissues and 48 clones from cancer cells of env gene sequences belonging to the HERV-H family showed 84.3-98.1% sequence similarity to that of HERV-H (AF108843). Deduced amino acid sequences of 60 clones from human tissues and cancer cell lines showed multiple frameshifts and termination codons caused by deletion/insertion or point mutation with the exception of eight clones as following: HHE9-1, HHE9-5 (skeletal muscle), HHE10-5 (spleen), CHE10-9 (MCF7), CHE12-4, CHE12-5 (MIA-PaCa-2), and CHE18-1, CHE18-3 (C-33A) to that of HERV-H (AF108843). A phylogenetic tree of the HERV-H family was constructed to understand their relationship, indicating that they were divided into three groups, one major (group I) and two minor (group II and III), through sequence divergence. The HERV-H families in group I has been proliferated on human genome during hominoid evolution. These active HERV-H elements are worthy of further investigations as potential pathogenic effects to various human diseases including cancers.

Amino Acid Sequence↗

PubMed2006

Phylogenetic analysis by RFLP and sequencing of mitochondrial DNA in a Korean population.

Analysis of molecular nature of mitochondrial DNA (mtDNA) could be powerful marker for anthropological studies of modern populations. While population genetic studies on mtDNA have been reported for several ethnic groups, no such study has been documented for the Korean population. We surveyed mtDNA polymorphisms in the HVS I of noncoding D-loop region and its upstream region from 430 unrelated healthy Korean population by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing analysis. PCR product with 2,790 bp spanning the specific mtDNA region (mt13715-16504) was subjected to RFLP analysis using 6 restriction enzyme (Hinf I, Hae III, Alu I, Dde I, Mbo I, Rsa I). On the PAUP analysis of PCR-RFLP results, 38 mtDNA haplotypes (Hap 1-38) were detected in the Korean populations, which were classified into 11 haplogroups (Grp 1-11) of related haplotypes encompassing all 38 haplotypes. In comparison of sequencing data with Anderson's reference sequence, the transition type was more prevalent than the transversion type. Insertions or deletions were not found. In addition, three of the polymorphic sites (A16240C, A16351G, G16384A) in HVS-I region are determined newly. The polymorphic sites were distributed randomly in the region, though the frequency at each site was variable. Thus, this research might be required for the genealogical study of Orientals.

Animals↗

PubMed2006

Endogenous retrovirus-related sequences provide an alternative transcript of MCJ genes in human tissues and cancer cells.

The MCJ gene is a member of the DNAJ family, and its transcriptional event is controlled by methylation of the CpG island. In our study, we found LTR33 and LTR7 elements provided an alternative transcript within the MCJ gene. To detect different expression patterns between the originally reported MCJ transcript and the LTR-related transcript, we performed a RT-PCR approach using various human tissues and cancer cells. The original MCJ transcript was detected in human tissues and cancer cells, whereas the LTR-related transcript was only revealed in some cancer cells (HCT106, MCF-3, TE-1, Hela, and CCHM). We also performed a PCR analysis to compare the insertion lineage of the LTR elements with the genomic DNAs of primates, indicating that those LTR33 and LTR7 elements of HERV-H have been integrated into the primate genome at different times. Taken together, we suggest that HERV-related elements trigger transcriptome diversification during primate evolution.

Base Sequence↗

PubMed2005

Analysis of newly identified low copy AluYj subfamily.

Human specific AluY elements were investigated by comparative analysis between human chromosome 21 and chimpanzee chromosome 22. Human specific AluY element was identified on human chromosome 21q22 (accession no. AL163282), and then that was a new member of AluYj subfamily. From the bioinformatic analysis, AluYj subfamily was investigated in human whole genome using AluYj4 consensus sequence (accession no. AL163282). Thirteen members of the AluYj4 elements (4 diagnostic mutations) and eight members of the AluYj3 elements (3 diagnostic mutations) were identified with distinct diagnostic mutation from AluY consensus sequence. The results of the molecular clock calculation of non-CpG region substitution indicated that, AluYj4 elements (2.1 million years old) may be proliferated more recent time than AluYj3 elements (14.1 million years old). For the verification of recent insertion time, four of AluYj4 elements (ch2-AC017101, ch10-AC044786, ch12-AC007656 and ch21-AL163282) from human chromosomes 2, 10, 12, 21 were analyzed by PCR amplification using various human and primate DNA samples. Though, no polymorphism was detected in human population, we identified the new AluYj4 subfamily as the human specific elements.

Alu Elements↗

PubMed2004

HESAS: HERVs Expression and Structure Analysis System.

SUMMARY: HESAS (HERVs Expression and Structure Analysis System) database was developed to understand the human endogenous retroviruses (HERVs) that have an effect on the expression of human functional genes. The database products are generated by the exon-based expressed sequence tag clustering and reconstructing of partial HERV structures that result from various mutations during primate evolution. The expression types were classified according to the existence of splicing, transcriptional start and polyadenylation signal sites. The database currently contains HERV information on 26,981 human genes of exon-intron structure. The HERV elements were inserted into 17,317 of these genes and linked to expression with 898 genes. AVAILABILITY: http://www.primate.or.kr/HESAS CONTACT: khs307@pusan.ac.kr.

Algorithms↗

PubMed2004

Human endogenous retroviral elements belonging to the HERV-S family from human tissues, cancer cells, and primates: expression, structure, phylogeny and evolution.

A new human endogenous retrovirus family (HERV-S) was recently identified from the human chromosome X. The HERV-S was 6.7 kb in length with typical retroviral structure (LTR-gag-pol-env-LTR). We investigated pol fragments of HERV-S family in various human tissues and cancer cells. The pol gene was expressed in only brain and thymus among human tissues (brain, prostate, testis, heart, kidney, liver, lung, placenta, skeletal muscle, spleen, thymus, uterus), whereas the pol gene was detected in various cancer cell lines (RT4, PFSK-1, BT-474, HCT-116, Jurkat, HepG2, MCF7, OVCAR-3, MIA-PaCa-2, PC3, LOX-IMVI, AZ521, 2F7, and C-33A) except for TE-1, UO-31, A549, and U-937 by RT-PCR analysis. Expression and sequencing data of the 33 clones imply that the pol gene of HERV-S family is more active in cancer cells than in human tissues, which may have transcriptional potential role related to various human cancers. Phylogenetic analysis of HERV-S pol family distinctively divided into three groups (group I, II, and III) through evolutionary divergence in primate evolution. Evolutionary divergence of the HERV-S family by PCR amplification and sequence analysis indicated that they were integrated into the primate genomes approximately 43 Myr ago and have been evolved rate of 0.3% nucleotide differences per Myr during primate evolution.

Amino Acid Sequence↗

PubMed2004

The distribution and expression of HERV families in the human genome.

The families of human endogenous retroviruses (HERVs) are widely distributed in the human genome. Here we examined their distribution and expression. Approximately forty thousand HERV elements including truncated and solitary long terminal repeats (LTRs) were identified. These elements were most dense on chromosomes 4, 20, X, and Y. From an analysis of genomic stability during primate evolution, the 5 cent -LTR of the HERV genome (5 cent LTR - internal HERV - 3 cent LTR) appeared to be more often truncated than the 3 cent -LTR. ESTs derived from normal placenta, skeletal muscle, hypothalamus, and testis gave frequent matches to HERV elements. We present a classification of genes associated with HERV elements according to the hierarchical structure of gene ontology.

Endogenous Retroviruses↗

PubMed2004

Expression analysis of endogenous retroviral elements belonging to the HERV-F family from human tissues and cancer cells.

Based on the primer binding site for Phe-tRNA, human endogenous retroviruses (HERVs) have been classified as HERV-F family members, HERV-F, HERV-FXA, HERV-Fb, and HERV-Fc. The HERV-F family was expressed in human placenta preferentially. We investigated pol fragments of HERV-F family in various human tissues and cancer cells. The pol gene was expressed in human placenta only among tissues (brain, prostate, testis, heart, kidney, liver, lung, placenta, skeletal muscle, spleen, thymus, uterus), but detected in various cancer cell lines (RT4, BT-474, HCT-116, TE-1, UO-31, Jurkat, A549, MCF7, OVCAR-3, MIA-PaCa-2, PC3, LOX-IMVI, AZ521, 2F7, U-937, and C-33A) except for PFSK-1 and HepG2 by RT-PCR analysis. Expression and sequencing data of the 37 clones imply that the pol gene of HERV-F family is active in cancer cells, which may have potential role related to cancer development.

Amino Acid Sequence↗

PubMed2004

Evolutionary implication of human endogenous retrovirus HERV-H family.

The human endogenous retrovirus (HERV-H) family is most abundant and widely distributed in the human genome, with about 100-1,000 full-length or deleted elements and a similar number of solitary, long-terminal repeats. The HERV-H env ORF has been characterized in humans and in the course of primate evolution, indicating the increased possibility of biological roles in humans. Using the polymerase chain reaction approach with a human monochromosomal DNA panel, 70 env fragments belonging to the HERV-H family from chromosomes 1, 2, 3, 4, 5, 6, 7, 9, 10, 11, 12, 14, 15, 16, 17, 18, 19, 20, X, and Y were identified and analyzed. They showed 82-99% sequence similarity to that of HERV-H (accession no. AF108843). We also identified other HERV-H env fragments in the DDBJ/EMBL/GenBank databases. The total of 120 fragments was evolutionarily analyzed. Phylogenetic analysis suggests that the HERV-H env family is divided into one major and two minor groups. The HERV-H members have been actively proliferated and evolved by intra-chromosomal spread during hominid radiation.

Chromosomes↗

PubMed2004

A prevalent POLG CAG microsatellite length allele in humans and African great apes.

The human nuclear gene for the catalytic subunit of mitochondrial DNA polymerase gamma ( POLG) contains within its coding region a CAG microsatellite encoding a polyglutamine repeat. Previous studies demonstrated an association between length variation at this repeat and male infertility, suggesting a mechanism whereby the prevalent (CAG)(10) allele, which occurs at a frequency of >80% in different populations, could be maintained by selection. Sequence analysis of the POLG CAG microsatellite region of more than 1000 human chromosomes reveals that virtually all allelic variation at the locus is accounted for by length variation of the CAG repeat. Analysis of POLG from African great apes shows that a prevalent length allele is present in each species, although its exact length is species-specific. In common chimpanzee ( Pan troglodytes) a number of different sequence variants contribute to the prevalent length allele, strongly supporting the idea that the length of the POLG microsatellite region, rather than its exact nucleotide or amino acid sequence, is what is maintained. Analysis of POLG in other primates indicates that the repeat has expanded from a shorter, glutamine-rich sequence, present in the common ancestor of Old and New World monkeys.

Amino Acid Sequence↗

PubMed2004

Expression and identification of HERV-W family in Japanese monkeys (Macaca fuscata).

We investigated structural genes (gag, pol, env) of HERV-W family in the Macaca fuscata (Japanese monkey). Those genes are expressed in various tissues (testis, prostate, kidney, cerebellum, thymus, pancreas, intestine, stomach, ovary) of the Japanese monkey in RT-PCR and sequencing analyses. Nine clones for gag, thirty-one clones for pol and thirty-four clones for env fragments of the HERV-W family in monkey tissues were identified and analyzed. These clones showed a high degree of sequence similarity, 82.2-84.7% for gag, 88.4-91.7% for pol, and 90.8-95.4% for env, to those of HERV-W family. Translation to amino acids in all clones derived from the monkey indicated that they showed multiple interruptions of frameshifts and termination codons by deletion/insertion or point mutation. Identical sequences from different tissues of the monkey were found in env and pol clones of the HERV-W family.

Amino Acid Sequence↗