Abstract
The highly conserved homology cassette family (HOX) as well as 18 referenced long non-coding antisense transcripts (HOXATs) play vital roles in the development of some cancers. Nevertheless, their expression patterns as well as their association with cancer prognosis and the tumor microenvironment (TME) in pan-cancers are still unclear. Here, based on public databases, the expression levels of HOXATs, their prognostic potentials, and correlation with tumor mutation burden (TMB), immune cell infiltration, immune subtype, immune response-related genes, and stemness scores corresponding to 33 tumor types were analyzed systematically using R language. The results of the analysis indicated that different cancer tissues show different HOXAT expression profiles. Further, HOXAT expression showed association with cancer prognosis and immune and stemness regulation. Gene set enrichment analysis also demonstrated that HOXATs participate in cancer- and immune-related pathways, and based on their expression levels, HOTAIRM1 and HOXB-AS1 showed potential involvement in oncogenesis as well as possible involvement in immune regulation across a variety of cancer types. Further investigation also confirmed a significantly higher expression of HOXB-AS1 in GBM than in lower grade glioma tissues. Importantly, in vitro cell function experiments indicated that HOXB-AS1 supports cancer stem cell and plays a fundamental role in glioma metastasis. In conclusion, our results provide valuable resources that can guide the investigation of the mechanisms related to the role of HOXATs in cancers as well as therapeutic analysis in this regard.
Highlights
For Long non-coding RNA stemness scores (RNAss), as one of the key regulators of cancer, function as important molecular markers for cancer prognosis, and as markers of molecular characteristics at the pan-cancer level
To identify all the publications related to homeobox antisense transcripts (HOXATs) in patients with cancer, the PubMed database and Web of Science were searched for literature using the following terms, which correspond to 16 out of the 18 referenced non-coding antisense transcripts: HOXAIRM1, HOXA-AS3, HOXA10-AS, HOXA11-AS, HOTTIP, HOXB-AS1, HOXB-AS2, HOXB-AS3, HOXB-AS4, HOXC13-AS, HOXC-AS1, HOXC-AS2, HOXCAS3, HOTAIR, HAGLR, and HOXD-AS2
We analyzed the connection between the expression of HOXATs and prognosis in patients with cancer by exploring all published related literature
Summary
For Long non-coding RNAs (lncRNAs), as one of the key regulators of cancer, function as important molecular markers for cancer prognosis, and as markers of molecular characteristics at the pan-cancer level. The most recent studies suggest that CSCs represent another important component of the TME that have differentiation abilities to generate the original lineage cells for regulating tumor occurrence, development, recurrence, metastasis and drug resistance. Increasing evidence has indicated that lncRNAs play fundamental roles in the regulation of the immune microenvironment and are closely associated with the development and progression of various CSCs. For example, the lncRNA, NeST has been shown to be related to T-cell activation, and is critical for immune response regulation (Chen et al, 2019b), while the lncRNA, NRON has been shown to maintain a resting state of T cells by sequestering phosphorylated NFAT in the cytoplasm (Chen et al, 2020). It has been demonstrated that the lncRNA, lnc-sox, modulates CRC tumorigenesis by unbalancing TME (Chen et al, 2016), while the lncRNA, LINK-A functions as an oncogene that promotes tumor immune evasion by sensitizing T cells (Dong et al, 2018). Further studies on lncRNAs and their roles in the TME of different cancer types still require investigation
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