title: LncRNA HOTAIR promotes cisplatin resistance in gastric cancer by targeting miR-126 to activate the PI3K/AKT/MRP1 genes.
abstract: Altered expression of long noncoding RNAs (lncRNAs) has shown to associate with human cancer development and progression and drug resistance. LncRNA HOX antisense intergenic RNA (HOTAIR) regulates chromatin state and highly expressed in various human cancers. This study analyzed HOTAIR expression in gastric cancer cells and tissues and then assessed the effects of HOTAIR on modulation of gastric cancer cell sensitivity to cisplatin and the underlying molecular events. The data showed that HOTAIR was significantly upregulated in cisplatin-resistant gastric cancer cells and tissues compared with control cells and noncancerous gastric tissues. Overexpression of HOTAIR enhanced gastric cancer cell proliferation, promoted cell cycle G1/S transition, but decreased tumor cell apoptosis. Furthermore, HOTAIR was shown to directly bind to and inhibit miR-126 expression and then to promote VEGFA and PIK3R2 expression and activate the PI3K/AKT/MRP1 pathway. In conclusion, the data demonstrated that high HOTAIR expression acted as a competitive endogenous RNA to promote cisplatin resistance in gastric cancer. Further study will evaluate HOTAIR expression as a biomarker to predict treatment response of cisplatin and explore inhibition of HOTAIR expression as a novel strategy for anti-cisplatin resistance in human gastric cancer.
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Gulou District, Nanjing, Jiangsu, 210000, China.|The First Clinical Medical College, Nanjing Medical University, Nanjing, Jiangsu, 210029, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Gulou District, Nanjing, Jiangsu, 210000, China.|The First Clinical Medical College, Nanjing Medical University, Nanjing, Jiangsu, 210029, China.
authors.forename: Yini
authors.initials: Y
authors.lastname: Dang
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Gulou District, Nanjing, Jiangsu, 210000, China.|The First Clinical Medical College, Nanjing Medical University, Nanjing, Jiangsu, 210029, China.|Department of Gastroenterology, The No. 1 People's Hospital of Xuzhou, Xuzhou, Jiangsu, 221009, China.
authors.forename: Shiyu
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Gulou District, Nanjing, Jiangsu, 210000, China.|The First Clinical Medical College, Nanjing Medical University, Nanjing, Jiangsu, 210029, China.
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Gulou District, Nanjing, Jiangsu, 210000, China. guoxinz@njmu.edu.cn.|The First Clinical Medical College, Nanjing Medical University, Nanjing, Jiangsu, 210029, China. guoxinz@njmu.edu.cn.
authors.forename: Guoxin
authors.initials: G
authors.lastname: Zhang
keywords: Cisplatin resistance; Gastric cancer; HOTAIR; PI3K/AKT; miR-126