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Numerous studies have demonstrated that lncRNAs participate in regulatory networks of different cancers. Dysregulation of various lncRNAs such as DUXAP8, LINC00963, and FOXD2-AS1 has been reported in the development of various cancers. The aim of this study was investigation of the importance and potential roles of DUXAP8, LINC00963, and FOXD2-AS1 in ER+ breast cancer (BC). We examined the expression levels of DUXAP8, LINC00963, and FOXD2-AS1 in 71 luminal A and B tumor tissues and two luminal A cell lines (MCF7 and T47D) compared with adjacent non-tumor tissues and MCF10A cell line by qRT-PCR assay, respectively. For identifying the relation between three lncRNAs and luminal BC, bioinformatic analyses were performed using some databases and software including GENEVESTIGATOR software, GEPIA2, DAVID, REVIGO, STRING, lncATLAS, Kaplan-Meier plotter, starBase, and miRNet tool. The results showed the significant upregulation of all three lncRNAs in luminal A and B tumor specimens and cell lines. Upregulation of DUXAP8 and FOXD2-AS1 was significantly associated with progesterone receptor-positive (PR+) and p53 protein expression in luminal BC patients, respectively. Based on bioinformatic analyses, DUXAP8 can be considered as a prognostic biomarker for patients with luminal BC. DUXAP8, LINC00963, and FOXD2-AS1 are involved in several cancer-associated signaling pathways and multiple cancer-related processes. In addition, bioinformatic analyses indicated that LINC00963/hsa-mir-130a-3p/HSPA8 axis might have potential regulatory role in BC. In conclusion, dysregulation of DUXAP8, LINC00963, and FOXD2-AS1 can play roles in the development of luminal BC. They may exert their functions through involvement in some cancer signaling pathways and processes. In addition, they may interact with miRNAs like predicted interaction of LINC00963 with miR-130a-3p.

Background: Estrogen receptor-positive (ER+) breast cancer (BC) (luminal A and B subtypes) comprises up to 70% of all BC patients. LncRNAs can affect many biological and pathological processes, and dysregulation of them is related to human cancers. The potential role of lncRNA LINC00968 in ER+ BC is still unclear. Methods: We analyzed the LINC00968 expression across 44 paired luminal BC tissues from the TCGA-BRCA RNA sequencing dataset, and we used the GEPIA2 web server and GENEVESTIGATOR software, as well. The qRT-PCR assay was performed to confirm the LINC00968 expression in 71 paired luminal BC tissues and two luminal A cell lines (MCF7 and T47D). Moreover, to better understand the potential function of LINC00968 in luminal BC, multiple in silico data analyses have been done including co-expression, functional enrichment, and genetic alteration analyses. Results: The results of data analyses retrieved from BRCA dataset and databases revealed the significant downregulation of LINC00968 in luminal A and B BC. Also, the results of qRT-PCR in luminal BC tissues and cell lines confirmed the earlier data. LINC00968 expression was negatively associated with tumor stage and lymph node metastasis. Additionally, functional annotation analyses revealed that LINC00968 might be involved in vascular development and angiogenesis, extracellular matrix organization, and cell motility and migration. LINC00968 might have functions in some cancer-related signaling pathways, like the PPAR signaling pathway, small ligand GPCRs, etc. Conclusions: Our study found that LINC00968 may be a potential tumor suppressor gene in luminal BC. Downregulation of LINC00968 might promote tumorigenesis, invasion, and metastasis of luminal BC.

Background Luminal breast cancer (BC) is the most frequent subtype accounting for more than 70% of BC. LncRNAs, a class of non-coding RNAs with more than 200 nucleotides, are involved in a variety of cellular processes and biological functions. Abberant expression is related to the development of various cancers, such as breast cancer. LINC01133, ZEB1-AS1, and ABHD11-AS1 were reported to be dysregulated in different cancers. However, their expression level in luminal BC remains poorly known. The aim of the present study was to evaluate the potential roles of these lncRNAs in BC, especially in luminal subtypes. Methods A comprehensive analysis was performed using the Lnc2Cancer database to identify novel cancer-associated lncRNA candidates. After conducting a literature review, three novel lncRNAs named LINC01133, ZEB1-AS1, and ABHD11-AS1 were chosen as target genes of the present study. Quantitative real‐time polymerase chain reaction (qRT-PCR) was used to evaluate the expression level of the mentioned lncRNAs in both luminal BC tissues and cell lines. Then, the correlation of the three mentioned lncRNAs expression with clinicopathological characteristics of the patients was studied. Moreover, several datasets were used to discover the potential roles and functions of LINC01133, ZEB1-AS1 and ABHD11-AS1 in luminal subtype of BC. Results According to the qRT-PCR assay, the expression levels of LINC01133 and ZEB1-AS1 were decreased in luminal BC tissues and cell lines. On the other hand, ABHD11-AS1 was upregulated in the above-mentioned samples. The expression levels of LINC01133, ZEB1-AS1, and ABHD11-AS1 were not associated with any of the clinical features. Also, the results obtained from the bioinformatics analyses were consistent with qRT-PCR data. Functional annotation of the co-expressed genes with the target lncRNAs, protein–protein interactions and significantly enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways across luminal BC were also obtained using bioinformatics analysis. Conclusions Taken together, our findings disclosed the dysregulation of LINC01133, ZEB1-AS1, and ABHD11-AS1 in luminal BC. It was revealed that LINC01133 and ZEB1-AS1 expression was significantly downregulated in luminal BC tissues and cell lines, while ABHD11-AS1 was upregulated considerably in the mentioned tissues and cell lines. Also, bioinformatics and systems biology analyses have helped to identify the possible role of these lncRNAs in luminal BC. However, further analysis is needed to confirm the current findings.

Mesenchymal stem cells (MSCs) are multipotent cells beneficial in regenerative medicine and tissue repair. The therapeutic potential of MSCs for inflammatory diseases and conditions is partly due to secreted exosomes. Exosomes are one group of extracellular vesicles with 50–150 nm in diameter. They can carry numerous molecules and introduce them to the recipient cells to produce various biological effects. Macrophages are classified into M1 and M2 subtypes based on their activation states. M1 macrophages release pro-inflammatory factors like tumor necrosis factoralfa (TNF-α), interleukin1alfa (IL-1α), interleukin1beta (IL-1β), interleukin6 (IL-6), C-X-C motif chemokine ligand 9 (CXCL9), and C-X-C motif chemokine ligand 10 (CXCL10), while M2 macrophages secrete anti-inflammatory mediators including interleukin10 (IL-10), transforming growth factor beta (TGF-β), C-C motif chemokine ligand 1 (CCL1), C-C motif chemokine ligand 17 (CCL17), C-C motif chemokine ligand 18 (CCL18), and C-C motif chemokine ligand 22 (CCL22). This review summarizes the effect of MSC-derived exosomes in the polarization of M2 macrophages, which their anti-inflammatory and immunomodulatory properties are potentially effective in inflammation diseases and conditions such as central nervous system (CNS) diseases, autoimmune diseases, inflammatory bowel disease, cardiomyopathy, graftversushost disease, kidney, liver, lung, and skin injuries.

Background Luminal subtype is the most common subgroup of breast cancer (BC), accounting for more than 70% of this cancer. Long non-coding RNAs (lncRNAs) are a group of RNAs which play critical roles in diverse cellular processes. It is proved that dysregulation of them can contribute to the development of various cancers, including BC. LINC00961 was reported to be downregulated in several cancers, however, its expression level in BC remains largely unknown. The purpose of the present study was to investigate the possible role of LINC00961 in luminal A and B subtypes of BC. Methods To obtain novel lncRNAs associated with different cancers and differentially expressed lncRNAs (DElncRNAs) between BC tumor and normal tissues, Lnc2Cancer and GDC databases were used, respectively. After performing literature review, the expression level of the selected lncRNA (LINC00961) was evaluated in 79 luminal A and B BC specimens and adjacent non-cancerous tissues by Quantitative Reverse Transcription PCR (qRT-PCR). LINC00961 expression was also evaluated in two luminal A BC cell lines, compared to a normal breast cell line. The comparison of the differences between tumor and adjacent non-tumor samples was performed by paired sample t-test. Moreover, correlation analysis between LINC00961 expression and clinicopathological features was performed using the chi-square, fisher exact, and independent t-test. In order to investigate the possible roles of LINC00961 in luminal A and B BC, different bioinformatics analyses such as functional annotation of the LINC00961 co-expressed genes and protein–protein interaction (PPI) networks construction were also performed. Results LINC00961 was selected as a significant DElncRNA which had not been studied in BC. According to q-RT PCR assay, LINC00961 was downregulated in luminal BC tissues and cell lines. Its expression was correlated with smoking status and the age of menarche in luminal BC patients. Also, the results of the bioinformatics analysis were consistent with the data obtained from q-RT PCR assay. The final results indicated that LINC00961 might be involved in multiple cancer-associated pathways such as chemokine, Ras and PI3K–Akt signaling pathways, GPCR ligand binding, and signal transduction in luminal subtypes of BC. CDH5, GNG11, GNG8, SELL, S1PR1, CCL19, FYN, ACAN, CD3E, ACVRL1, CAV1, and PPARGC1A were identified as the top hub genes of the PPI networks across luminal subgroup. Conclusion Our findings suggested that LINC00961 was significantly downregulated in luminal A and B subtypes of BC. Moreover, bioinformatics analysis provided a basis for better identification of the potential role of LINC00961 in luminal subtype of BC.

Purpose Breast Cancer (BC) is the most frequent malignancy among women worldwide. ER+ breast cancers (luminal A and B subtypes) comprise up to 70% of all BC patients. Long non-coding RNAs (lncRNAs) are regulatory non-coding transcripts and longer than 200 nucleotides. LncRNAs can affect many biological and pathological processes and dysregulation of them is related to many human cancers. The potential role of LINC00968 lncRNA in luminal A and B breast cancer pathogenesis is still unclear. Methods Seventy-one pairs of tumor and adjacent non-tumor tissue specimens of luminal A and B breast cancer were used to analyze the expression of LINC00968. Furthermore, two luminal A cell lines, MCF7 and T47D, were used to evaluate the expression of LINC00968 compared with a non-malignant breast cell line, MCF10A. Moreover, we have done multiple bioinformatic analyses for a better understanding of the potential roles of LINC00968 in luminal BC. Results Our data revealed the significant downregulation of LINC00968 in luminal tumor tissues and cell lines. LINC00968 expression was negatively associated with tumor stage and lymph node metastasis. Bioinformatic analyses indicated that LINC00968 might be involved in blood vessel development, angiogenesis, and might be participated in interaction of ECM constituents with cancer cells. LINC00968 might have functions in some cancer-related signaling pathways, like PI3K/Akt, ECM-receptor interaction signaling pathway, and PPAR signaling pathway. Conclusions Downregulation of LINC00968 might promote carcinogenesis of luminal BC. LINC00968 might act as a tumor suppressor gene and might also promote invasion and metastasis of luminal BC.

Background: Breast Cancer (BC) is the most common cancer in women worldwide. Long non-coding RNAs (lncRNAs) are regulatory non-coding transcripts and longer than 200 nucleotides. lncRNAs can affect many biological and pathological processes and dysregulation of them is related and studied in many human diseases like, cancers. We performed this study to evaluate the probable functions of lncRNAs FOXD2-AS1 and LINC00968 in breast cancer. Methods: The tumor tissue and adjacent non-tumor tissue specimens of luminal A and B breast cancer (the most frequent subtypes of breast cancer) were used to analyze the expression of these two lncRNAs, using the qRT-PCR technique. Furthermore, two luminal A breast cancer cell lines, MCF7 and T47D, were used to evaluate the expression of FOXD2-AS1 and LINC00968 compared with control breast cell line, MCF10A. Because of the luminal subtypes are the most frequent subtypes of breast cancer and also the most common subtypes among breast cancer patients, the present study was generally focused on the luminal and breast cancer. Also, some in silico analyses were done according to some databases and software for better understanding about the potential functions of mentioned lncRNAs in breast cancer. Results: Our data indicated the significant upregulation and downregulation of FOXD2-AS1 and LINC00968, respectively, in tumor tissues and breast cancer cell lines (MCF7, T47D). The bioinformatic analyses confirmed the experimental results. FOXD2-AS1 expression was positively associated with p53 protein and LINC00968 expression was negatively associated with tumor stage and lymph node metastasis. According to our findings, LINC00968 might be function as a tumor suppressor gene in breast cancer and this lncRNA might function in some cellular signaling pathways, like PI3K/Akt and Ras signaling pathways based on the co-expressed genes, but more investigations are required. Conclusions: The two mentioned lncRNAs might play roles in breast cancer pathogenesis but more experimental studies are needed to explore the mechanisms of the functions of these two lncRNAs in breast cancer.

Additional file 3: Figure S3. LINC00961 expression level across 13 luminal A and B breast cancer cell lines, compared to 3 normal breast cell lines, obtained by GENEVESTIGATOR software.

Additional file 1: Figure S1. The baseline expression of LINC00961 across normal breast tissues, obtained using Gene Expression Atlas software.

Additional file 2: Figure S2. LINC00961 expression level across 12 breast cancer categories, including 1910 luminal A and B samples, compared to normal breast tissue, obtained by GENEVESTIGATOR software.

Additional file 9: Figure S5. The summarization of all GO terms related to biological process. Each node is a GO term and node color indicates the statistical significance of p‐value. Node size suggests how frequent the GO term is among the complete set. The summarization and visualization were done by the REViGO and Cytoscape, respectively.

Additional file 7: Figure S4. Differential LINC00961 expression analysis across different subtypes of breast cancer, obtained using TANRIC database.

Recently, ST18 polymorphism has played a role in increasing the risk of pemphigus among some populations such as Egyptian and Jewish. In addition, a variant within the ST18 promoter gene was shown to induce ST18 upregulation and cytokine secretion leading to keratinocyte susceptibility to anti-desmoglein antibodies. Thus, the present study aimed to assess the ST18 single nucleotide polymorphisms (SNP) relationship with pemphigus, disease severity and family history among Iranian population. A total of 111 pemphigus patients and 201 healthy controls were genotyped for three ST18 SNPs rs2304365, rs10504140 and rs4074067 by using TETRA-ARMS PCR method. The results indicated that risk allele A in rs2304365 was significantly higher in pemphigus patients, compared with the amount in the control group (OR = 2.43 CI = 1.49-3.975, P