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

Abstract

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. Graphical abstract

Landscape and functional repertoires of long noncoding RNAs in the pan-cancer tumor microenvironment using single-nucleus total RNA sequencing

“…2d). Furthermore, our analysis identifies OBI1-AS1 as a super-exclusive marker for astrocytes, corroborating previous findings reported by Mamivand et al 26 . The specific expression of OBIA-AS1 within astrocytes provides further evidence of its roles as a highly specific marker for this particular cell type (Fig.…”

Genome-wide screening for differentially methylated long noncoding RNAs identifies LIFR-AS1 as an epigenetically regulated lncRNA that inhibits the progression of colorectal cancer

“…Mamivand et al identified an epigenetically deregulated lncRNA OBI1-AS1 with decreased expression in glioblastoma multiforme. Hi-C and ChIP-Seq analysis showed that methylation of the CTCF binding site blocked the expression of OBI1-AS1 by influencing chromatin interactions [ 9 ]. LncRNAs also function as a scaffold for the recruitment of chromatin modifiers to target promoters.…”

Correlation research of susceptibility single nucleotide polymorphisms and the severity of clinical symptoms in attention deficit hyperactivity disorder

“…Several human genetic studies and animal studies also reported that genetic variations in the metabotropic glutamate receptor (mGluRs) subtype III may be associated with ADHD (47)(48)(49)(50)(51)(52)(53)(54). OBI1-AS1 expression has also been reported to be associated with astrocyte content, and some studies in recent years have attributed the pathophysiology of depression and mood disorders to astrocytes (45,(55)(56)(57). These can aid in the interpretation of our results to some extent, but our findings must be viewed with caution and be seen as preliminary.…”

“…Although the exact function of OBI1-AS1 remains unclear, several studies have suggested a regulatory role for the hybridization of natural antisense RNAs with endogenous mRNAs (43). Recent studies have reported that RNF219-AS1 was involved in the pathophysiology of ADHD (44), and that OBI1-AS1 has a potential role in glutamate receptor signaling and synaptic responses (45). Previous studies have linked genetic variations in the ion glutamate receptor to ADHD risk (46).…”