Onco-lncRNA HOTAIR and its functional genetic variants in papillary thyroid carcinoma

Abstract

The role of long noncoding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) and its functional single nucleotide polymorphisms (SNPs) in papillary thyroid carcinoma (PTC) is still largely unclear. Therefore, we investigated the involvement of lncRNA HOTAIR and its three haplotype-tagging SNPs (htSNPs) in PTC. There was higher expression of HOTAIR in PTC tissues compared to normal tissues. A series of gain-loss assays demonstrated that HOTAIR acts as a PTC oncogene via promoting tumorigenic properties of PTC cells. Additionally, the functional HOTAIR rs920778 genetic variant was a PTC susceptibility SNP. Subjects with the HOTAIR rs920778 TT genotype had an odds ratio (OR) of 1.88, 1.25 and 1.61 (P = 6.0 × 10−6, P = 0.028 and P = 3.2 × 10−5) for developing PTC in Shandong, Jiangsu and Jilin case-control sets compared with subjects with the CC genotype. This statistically significant associations were only found between the rs920778 genetic polymorphism and PTC risk in females but not in males. The allele-specific regulation on HOTAIR expression by the rs920778 SNP was confirmed both in vitro and in vivo. Our results demonstrate that functional SNPs influencing lncRNA regulation may explain a part of PTC genetic basis.

lncRNA SNHG5 is associated with poor prognosis of bladder cancer and promotes bladder cancer cell proliferation through targeting p27

“…Accumulating documents have demonstrated that the dysregulation of lncRNAs are associated with tumorigenesis and progression of malignant tumors (18)(19)(20)(21)(22)(23). For instance, Zhou et al demonstrated that downregulation of lncRNA MEG3 mediated by DNMT3b contributed to nickel malignant transformation of human bronchial epithelial cells via modulating PHLPP1 transcription and HIF-1alpha translation (11).…”

Non-coding RNAs: long non-coding RNAs and microRNAs in endocrine-related cancers

“…Analysis of data in the Cancer Genome Atlas (TCGA) revealed that increased HOTAIR expression correlates with metastasis and poor prognosis in breast and prostate cancers (Weidle, et al 2017). HOTAIR is both nuclear and cytoplasmic and considered an onco-lncRNA because of its ability to promote papillary thyroid cancer (PTC) cell proliferation and silencing its expression inhibited cell growth (Zhu, et al 2016). HOTAIR is a scaffold for the PRC2 and LSD1 complexes affecting H3K27 methylation and H3K4 demethylation for epigenetic gene silencing promoting cancer metastasis .…”

“…HOTAIR is upregulated in endometrial cancer (EC) (Smolle, et al 2015) and contributes to cisplatin-resistance by inhibiting autophagy (Sun, et al 2017b). HOTAIR is highly expressed in ovarian cancer (Luo, et al 2017), in endometrial, ovarian, and cervical cancers (Li, et al 2017a), and in thyroid cancers ), including PTC (Zhu et al 2016).…”

LncROR Promotes Bladder Cancer Cell Proliferation, Migration, and Epithelial-Mesenchymal Transition

“…Many lncRNAs, such as MALAT1, H19, and HOTAIR have been demonstrated as critical regulator of carcinogenesis and development of many cancers [8-12]. LncROR was first discovered in induced pluripotent stem cells (iPSCs).…”