HOXA11-AS1
HOXA11-AS lncRNA is a
The HOX genes code for
Function
Many lncRNAs are sequences that regulate the expression of nearby or distant genes. Common in HOX genes, lncRNAs can either regulate through
HOXA11-AS is similar to other lncRNAs in that it can affect many genes at once, thus allowing both local and genome-wide control.[6] It is also similar because of its function in regulating cell proliferation, cell cycle, migration, apoptosis, and promoting angiogenesis.[1] Some studies have shown that overexpression causes aberrant functions of the mechanisms listed above; however, other studies have shown downregulation is the cause.[1][5]
Mechanism
Not much is known about the exact mechanism of HOXA11-AS lncRNA.
Epigenetic proteins that are involved with lncRNAs are categorized as either: writers, readers, or erasers.[6] These proteins either add epigenetic modifications, recognize epigenetic changes, or remove epigenetic modifications, respectively. LncRNAs are able to complementarily hybridize to DNA sequences in the genome, thus targeting sequences and localizing epigenetic changes.[10] Oftentimes, lncRNAs are not free-floating in the nucleus and are attached to chromosomes.[2]
Studies regarding HOX genes have found that lncRNAs are highly expressed in relation to the
Cancer Research
HOXA11-AS has been reported to have roles in various different cancers, including
Breast Cancer
Tissue samples of patients with breast cancer show high expression levels of HOXA11-AS, indicating its carcinogenic nature.[7][12] Evidence of over-expression of HOXA11-AS as a causative factor of cell proliferation is seen when proliferation is blocked, once the lncRNA expression is knocked-down, or removed. Manipulating or removing the expression of this lncRNA allowed scientists to halt the progression of the cell cycle and initiate cell apoptosis at common cellular checkpoints, such as G1/G0 stage.[7][12] The expression of the lnRNA was also suppressed by using small interfering RNAs (siRNA), that would degrade HOXA11-AS lnRNA transcripts. Upon doing so, cell proliferation was blocked.[7] In addition to interfering with proliferation, degradation of HOXA11-AS lncRNA with siRNA was also seen to influence cell migration and cell tumor invasion, which is cancer metastasis.[7][12] Scientists were able to determine these effects of HOXA11-AS lncRNA on breast cancer by monitoring the changes of epithelial-mesenchymal markers in the cell. Current research is looking at the potential possibility that breast cancer can be controlled or blocked by regulating the interaction between the lnRNA and epithelium/mesenchyme.[12]
Lung Cancer
In
Ovarian Cancer
HOXA11-AS lncRNA is studied in cancer research since its over-expression has been reported in epithelial ovarian cancer (EOC). In addition, on the molecular level, single nucleotide polymorphisms (SNPs) have also been observed in the lncRNA sequences of HOXA11-AS in EOC patients. Studies have shown that the SNP variants in these lncRNA sequences do not increase risk of EOC in patients, but may be the driving force of the cancer phenotype.[5]
Regularly, HOXA11-AS lncRNA is a tumor-suppressor that inhibits EOC proliferation and migration; however, in many EOC cases, researchers observed downregulation of the lncRNA in the ovarian tissue.
Gastric Cancer
HOXA11-AS has been shown to be significantly up-regulated in
Colorectal Cancer
Tissue samples from patients with colorectal cancer (CRC) were observed to have decreased expression of HOXA11-AS lnRNA when compared to normal colon cells.[8] Correlations were seen between patients with larger tumor size, higher carcinoembryonic antigen (CEA), and increased metastases to decreased expression of the lncRNA.[8] These metastases were tumor-node metastases (TNM) and lymphatic metastases. Lymphatic metastases is significant, as it is a common route for cancer cells to migrate to other parts of the body.[15] Scientists were able to determine the effect HOXA11-AS lnRNA had on migration by blocking the transcript with siRNA and observing decreased cell migration and invasion.[16] There was no correlation found between the migration distance and decreased HOXA11-AS lnRNA expression.[8]
See also
- Long noncoding RNA