HOTAIR overexpression may promote tumor invasiveness and progression in ESCC, given that HOTAIR functions as a miR-130a-5p sponge, positively regulating ZEB1.
We highlight the molecular mechanisms by which HOTAIR could influence the expression of Hexokinase 2 (HK2) in ESCC through binding miR-125 and miR-143 directly.
HOTAIR mRNA expression levels were significantly higher in ESCC compared with in para-carcinoma tissues, and HOTAIR mRNA expression levels were significantly higher in the groups with lymph node involvement or organ metastasis compared with the group without.
Effects of irradiation on radioresistance, HOTAIR and epithelial-mesenchymal transition/cancer stem cell marker expression in esophageal squamous cell carcinoma.
Moreover, there was a significant correlation between serum HOTAIR expression and the expression of HOTAIR in ESCC tissue according to Pearson correlation analysis.
The subgroup analysis suggested that the elevated levels of HOTAIR appears to be worse OS in Asian population (HR=2.06, 95% CI 1.80-2.37, P<0.00001) and digestive system cancers (HR=2.27, 95% CI 1.93-2.67, P<0.00001) including esophageal squamous cell carcinoma (HR=2.27, 95% CI 1.62-3.18, P<0.00001) and colorectal cancer (HR=4.65, 95 % CI 2.39-9.05, P<0.00001).
Moreover, subgroup analysis revealed that HOTAIR overexpression was also markedly associated with short survival for esophageal squamous cell carcinoma (HR 2.19, 95 % CI 1.62-2.94) and gastric cancer (HR 1.66, 95 % CI 1.02-2.68).
Moreover, there is an allelic regulation of rs920778 on HOTAIR expression via this enhancer in both ESCC cell lines and normal esophageal tissue specimens, with higher HOTAIR expression among T allele carriers.
Full elucidation of HOTAIR functionality relevant to ESCC may open avenues for the use of lncRNAs in identification of novel drug targets and therapies for ESCC and other prevalent cancers.
The knockdown of HOTAIR in the KYSE510 and KYSE180 ESCC cell lines using small hairpin RNAs (shRNAs) reduced the ability of the cells to form foci, migrate, and invade the extracellular matrix in culture, altered cell cycle progression, and increased the sensitivity of the cells to apoptosis.