An insight into the potential role of LINC00968 in luminal breast cancer: Case-control study and bioinformatics analysis.

Background: Luminal A and B subtypes of breast cancer (BC) 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 luminal BC is still unclear. Materials and methods: We analyzed the LINC00968 expression across 44 paired luminal BC tissues from the TCGA-BRCA RNA sequencing dataset. Besides, we used the GEPIA2 web server and GENEVESTIGATOR software, as well. Real-Time Quantitative Reverse Transcription PCR (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 understanding the potential role of LINC00968 in luminal BC, computational data analyses including co-expression analysis, functional annotation analysis, and genetic alteration analysis have been done. 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 play role in some cancer-related signaling pathways. Conclusion: Our study found that downregulation of LINC00968 might promote tumorigenesis, invasion, and metastasis of luminal BC.

A patient with PLACK syndrome with a novel splicing mutation in CAST: the evidence for a loss-of-function mechanism through mis-splicing.

PLACK syndrome is a relatively recently defined generalized peeling skin syndrome that has been reported with major skin manifestations and sometimes atypical features. We report the case of a 5-year-old boy with PLACK manifestations. Whole exome sequencing and subsequent Sanger sequencing identified a putative splice variant c.1209+2T>G in CAST (NM_001042440.5). Moreover, mRNA sequencing confirmed the abnormal alternative splicing of the CAST gene, leading to the addition of one nucleotide to the correct open-reading frame at the mRNA level. Segregation and expression analysis revealed that this loss-of-function via mRNA nonsense-mediated decay could be the causative pathogenic mechanism responsible for this patient's phenotype. This study extends our understanding of the various phenotypic and genotypic features of PLACK syndrome.

Data mining of bulk and single-cell RNA sequencing introduces OBI1-AS1 as an astrocyte marker with possible role in glioma recurrence and progression.

Long non-coding RNAs (LncRNAs) are widely known for their various functions in cancer from tumor initiation to tumor progression and metastasis. Gliomas are the most prevalent primary forms of brain tumor, classified into grades I to IV according to their malignant histological features with grade IV, also known as glioblastoma multiforme (GBM), displaying the highest level of malignancy. Thus, the search for differentially expressed LncRNAs in GBM versus low-grade glioma to uncover new insights into the molecular mechanisms of glioma progression have intensified. Bulk RNA sequencing pinpointed decreased expression of OBI1-AS1 in GBM compared to low-grade glioma samples. Subsequent single nuclei RNA sequencing revealed OBI1-AS1 to be a super-exclusive astrocyte marker with AUC = 0.99 and the potential to fully differentiate astrocytes from other brain cell types. Additional supplementary bioinformatics analysis exhibited OBI1-AS1 role in synaptic signal transduction and glutamatergic signaling. In addition, ChIP-Seq data were analyzed to explore transcription factors that can regulate OBI1-AS1 expression in neural cells. Results of Hi-C, methylation and ChIP-Seq analysis strongly suggest methylation of the CTCF binding site serving a central role in regulation of OBI1-AS1 expression via managing chromatin interactions. Our study indicated that lncRNAs, like OBI1-AS1, could be extremely precise in identifying the astrocyte cluster in the single-cell transcriptome and demonstrating superiority to well-established astrocyte markers such as GFAP, S100B, ALDH1L1, and AQP4.

Differential Expression of Hypoxia-Related Genes in Primary Brain Tumors and Correlation with Clinicopathologic Data.

OBJECTIVE: Meningiomas and gliomas are common benign and malignant primary brain tumors, respectively. One of the most prominent features of aggressive malignancies contributing to their progression is their ability to cope with hypoxia. Therefore, glioma tumors are expected to better cope with adverse hypoxic conditions and, consequently, display significantly different expression levels of hypoxia-adaptive genes. METHODS: Thirty-three glioma (17 glioblastoma multiforme [GBM], 16 low-grade glioma [LGG]) and 32 meningioma samples were investigated for expression of hypoxia adaptation- related genes by real-time polymerase chain reaction. The same investigation was carried out for GBM, the most malignant form of glioma, versus LGG. The findings were further checked by bioinformatics analysis of expression levels using RNA-seq data. Additional investigations conducted include receiver operating characteristic curve analysis to assess the power for each gene in differential diagnosis of glioma from meningioma. RESULTS: A greater level of hypoxia-inducible factor (HIF) 1α expression in glioma samples compared with meningioma and greater expression levels of Yes-associated protein (YAP) 1 and G-protein-coupled receptor class C group 5 member A (GPRC5A) in meningioma were observed, with P values 0.0005, <0.0001, and <0.0001 for GPRC5A, HIF1α, and YAP1, respectively. Comparison of GBM with LGG also revealed GPRC5A to have significantly greater expression in GBM with P = 0.0381. The calculated area under the curve was 0.7536, 0.8438, and 0.8272 for GPRC5A, HIF1α, and YAP1, respectively, which represented acceptable power for these genes in differential diagnosis of glioma tumor types from meningioma and tumor subtypes GBM from LGG under study. CONCLUSIONS: These results imply that these genes can possibly be implicated in brain tumor hypoxia-adaptation response with tumor-specific roles and patterns of expression.