Genomic analysis uncovers that cold-inducible RNA binding protein is associated with estrogen receptor in breast cancer.

BACKGROUND: RNA-binding proteins (RBPs) perform various biological functions in humans and are associated with several diseases, including cancer. Therefore, RBPs have emerged as novel therapeutic targets. Although recent investigations have shown that RBPs have crucial functions in breast cancer (BC), detailed research is underway to determine the RBPs that are closely related to cancers. OBJECTIVE: To provide an insight into estrogen receptor (ER) regulation by cold-inducible RNA binding protein (CIRBP) as a novel therapeutic target. RESULTS: By analyzing the genomic data, we identified a potential RBP in BC. We found that CIRBP is highly correlated with ER function and influences clinical outcomes, such as patient survival and endocrine therapy responsiveness. In addition, CIRBP influences the proliferation of BC cells by directly binding to ER-RNA. CONCLUSION: Our results suggest that CIRBP is a novel upstream regulator of ER and that the interplay between CIRBP and ER may be associated with the clinical relevance of BC.

Integrative analysis of RNA-sequencing and microarray for the identification of adverse effects of UVB exposure on human skin.

Background: Ultraviolet B (UVB) from sunlight represents a major environmental factor that causes toxic effects resulting in structural and functional cutaneous abnormalities in most living organisms. Although numerous studies have indicated the biological mechanisms linking UVB exposure and cutaneous manifestations, they have typically originated from a single study performed under limited conditions. Methods: We accessed all publicly accessible expression data of various skin cell types exposed to UVB, including skin biopsies, keratinocytes, and fibroblasts. We performed biological network analysis to identify the molecular mechanisms and identify genetic biomarkers. Results: We interpreted the inflammatory response and carcinogenesis as major UVB-induced signaling alternations and identified three candidate biomarkers (IL1B, CCL2, and LIF). Moreover, we confirmed that these three biomarkers contribute to the survival probability of patients with cutaneous melanoma, the most aggressive and lethal form of skin cancer. Conclusion: Our findings will aid the understanding of UVB-induced cutaneous toxicity and the accompanying molecular mechanisms. In addition, the three candidate biomarkers that change molecular signals due to UVB exposure of skin might be related to the survival rate of patients with cutaneous melanoma.

Distributions of 11-loci HLA alleles typed by amplicon-based next-generation sequencing in South Koreans.

The range of HLA typing for successful hematopoietic stem cell transplantation (HSCT) is gradually expanding with the next-generation sequencing (NGS)-based improvement in its quality. However, it is influenced by the allocation of finances and laboratory conditions. HLA-A, -B, -C, -DRB1/3/4/5, -DQA1, -DQB1, -DPA1, and -DPB1 alleles were genotyped at the 3-field level by amplicon-based NGS using MiSeqDx system and compared to our previous study employing long-range PCR and NGS using TruSight HLA v2 kit, in healthy donors from South Korea. Exon 2, exons 2/3, exons 2/3/4 or 5 of 11-loci were amplified by multiplex PCR. The sequence reads of over 53 depth counts were consistently obtained in each sample exon, depending on the target exon determined to match the reference sequence contained in the IPD-IMGT/HLA Database. HLA alleles were investigated by combinations of the determined exons. A total of 18 alleles with a frequency over 10% were found at the 11 HLA loci. Three ambiguities of HLA-A, -C, and -DRB1 were resolved. We observed a total of 26 HLA-A ~ C ~ B and 6 HLA-DRB1 ~ DQA1 ~ DQB1 ~ DPA1 ~ DPB1 haplotypes having significant linkage disequilibrium between alleles at all neighboring HLA loci. This result was compatible with the previous one, using TruSight HLA v2 kit. Advantages are simple and short progress time because one plate is used for each PCR step in one PCR machine and 11-loci HLA typing is possible even if only eight samples. These data suggested that expanded 11-loci HLA typing data by amplicon-based NGS might help perform HSCT.

Gastric CD56-negative Extranodal Natural Killer/T-cell Lymphoma: A Case Report.

Extranodal natural killer (NK)/T-cell lymphoma, nasal type (ENKTCL-NT) is the most common subtype of Epstein-Barr virus-associated NK/T-cell lymphomas. ENKTCL-NT occurs infrequently in the gastrointestinal tract. In particular, reports of ENKTCL-on NT arising from the stomach are extremely rare. Several clusters of differentiation (CDs) have been useful in recognizing NK-cells, T-cells, and tumor cells of NK/T-cell lymphomas. Among them, the CD56 antigen is considered the most sensitive marker for ENKTCL-NT and is expressed in almost all cases of ENKTCL-NT. Thus, the development of CD56-negative ENKTCL-NT is highly atypical. This paper reports a case of a young Asian female who presented with gastric ulcer bleeding. The patient was histologically diagnosed with ENKTCL-NT. No tumor cells for CD56 were observed, whereas no monoclonality of the T-cell receptor gamma gene rearrangement was detected in the tumor cells. The patient was scheduled for systemic chemotherapy six times and achieved complete remission. Peripheral blood-hematopoietic stem cell transplantation was performed later.

The HLA-B*07:457 allele identified in a volunteer donor for hematopoietic stem cell transplant.

HLA-B*07:457 differs from HLA-B*07:02:01:01 in codon 117 in exon 3.

The HLA-DRB1*12:97 allele identified in a volunteer donor for hematopoietic stem cell transplant.

HLA-DRB1*12:97 differs from HLA-DRB1*12:02:01:01 in codon 63 in exon 2.

The HLA-B*51:353 allele identified in a volunteer donor for hematopoietic stem cell transplant.

HLA-B*51:353 differs from HLA-B*51:01:01:01 in codon 95 in exon 3.

The HLA-B*13:144 allele identified in a volunteer donor for hematopoietic stem cell transplant.

HLA-B*13:144 differs from HLA-B*13:01:01:01 in codon 12 in exon 2.

The HLA-A*24:514N allele identified in a volunteer donor for hematopoietic stem cell transplant.

HLA-A*24:514N differs from HLA-A*24:02:01:01 in codon 167 in exon 3.

The HLA-A*02:954 allele identified in a volunteer donor for hematopoietic stem cell transplant.

HLA-A*02:954 differs from HLA-A*02:06:01:01 in codon 82 in exon 2.

The HLA-DRB1*09:45 allele identified in a volunteer donor for hematopoietic stem cell transplant.

HLA-DRB1*09:45 differs from HLA-DRB1*09:01:02:01 in codon 19 in exon 2.

The HLA-A*11:384 allele identified in a volunteer donor for hematopoietic stem cell transplant.

HLA-A*11:384 differs from HLA-A*11:01:01:01 in codon 151 in exon 3.

The HLA-B*35:01:64 allele identified in a volunteer donor for hematopoietic stem cell transplant.

HLA-B*35:01:64 differs from HLA-B*35:01:01:01 in codon 58 in exon 2.

Distributions of HLA-A, -B, and -DRB1 alleles typed by amplicon-based next generation sequencing in Korean volunteer donors for unrelated hematopoietic stem cell transplantation.

HLA genes play a pivotal role for successful hematopoietic stem cell transplantation (HSCT). There is an increasing need for sophisticated screening of donor HLA genotypes for unrelated HSCT. Next generation sequencing (NGS) has emerged as an alternative for classical Sanger sequence for HLA typing. In this study, HLA-A, -B, and -DRB1 alleles were genotyped at the allelic (6-digit) level using MiSeqDx in 26,202 volunteers from the Korean Network for Organ Sharing. Exon 2 and 3 of HLA-A and -B and exon 2 of HLA-DRB1 were amplified by polymerase chain reaction (PCR) and each allele was determined by matching the targeted exons and the reference sequence consisting of the IPD-IMGT/HLA Database. Seventy alleles of HLA-A, 102 alleles of HLA-B, and 69 alleles of HLA-DRB1 were identified. According to common and well-documented catalogs, 34 alleles in HLA-A, 61 in HLA-B, and 45 in HLA-DRB1 locus were common alleles, and 12, 14, and 11 kinds, were well-documented alleles, respectively. Thirteen novel alleles including 3 alleles in HLA-A, 8 alleles in HLA-B, and 2 alleles in HLA-DRB1 loci were found. Ten haplotypes with a frequency of more than 1.0% accounted for 22.4% of the total haplotype frequencies. Cis/trans ambiguities of HLA-A and -B loci by combination of exons 2 and 3 were analyzed to be 0.17% of 3 and 3.95% of 22 genotypes, respectively. This information on rare and novel alleles found by accurate HLA typing with NGS may be helpful for unrelated HSCT among Koreans.

The HLA-A*24:480 allele identified in a volunteer donor for hematopoietic stem cell transplant.

HLA-A*24:480 differs from HLA-A*24:02:01:01 in codon 178 in exon 3.

The HLA-DRB1*04:05:21 allele identified in a volunteer donor for hematopoietic stem cell transplant.

HLA-DRB1*04:05:21 differs from HLA-DRB1*04:05:01:01 in codon 83 in exon 2.

The HLA-A*33:03:42 allele identified in a volunteer donor for hematopoietic stem cell transplant.

HLA-A*33:03:42 differs from HLA-A*33:03:01:01 in codon 90 in exon 2.

Extracellular Vesicles Derived from Senescent Fibroblasts Attenuate the Dermal Effect on Keratinocyte Differentiation.

The skin is a multilayered and primary defensive organ. Intimate intercellular communication in the skin is necessary to ensure effective surveillance. Extracellular vesicles (EVs) are being explored for their involvement in intercellular skin communication. The aim of this study was to evaluate how human dermal fibroblasts (HDFs) accelerate EV production during senescence and the effects of senescence-associated EVs on epidermal homeostasis. Replicative senescent HDFs were assessed with senescence-associated ß-galactosidase staining and the expression of senescence-related markers. Isolated EVs were characterized by dynamic light scattering and EV marker expression. EVs secreted from untreated young or senescent HDFs, or from those treated with a nSMase inhibitor, antioxidant, and lysosomal activity regulators, were determined by sandwich ELISA for CD81. Human epidermal keratinocytes were treated with young- and senescent HDF-derived EVs. Compared to young HDFs, senescent HDFs produced relatively high levels of EVs due to the increased nSMase activity, oxidative stress, and altered lysosomal activity. The nSMase inhibitor, antioxidant, and agents that recovered lysosomal activity reduced EV secretion in senescent HDFs. Relative to young HDF-derived EVs, senescent HDF-derived EVs were less supportive in keratinocyte differentiation and barrier function but increased proinflammatory cytokine IL-6 levels. Our study suggests that dermis-derived EVs may regulate epidermal homeostasis by reflecting cellular status, which provides insight as to how the dermis communicates with the epidermis and influences skin senescence.

The HLA-B*46:01:26 allele identified in a volunteer donor for hematopoietic stem cell transplant.

HLA-B*46:01:26 differs from HLA-B*46:01:01:01 in codon 66 in exon 2.

The HLA-A*31:154 allele identified in a volunteer donor for hematopoietic stem cell transplant.

HLA-A*31:154 differs from HLA-A*31:01:02:01 in codon 115 in exon 3.