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Tumor Biology

, Volume 37, Issue 12, pp 16345–16355 | Cite as

LncRNA HOTAIR promotes cisplatin resistance in gastric cancer by targeting miR-126 to activate the PI3K/AKT/MRP1 genes

  • Jin Yan
  • Yini Dang
  • Shiyu Liu
  • Yifeng Zhang
  • Guoxin Zhang
Original Article

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.

Keywords

Gastric cancer HOTAIR miR-126 PI3K/AKT Cisplatin resistance 

Notes

Acknowledgments

This work was supported in part by grants from the National Natural Science Foundation of China (#81270476 and #81470830), Jiangsu Standard Diagnosis and Treatment Research Projects for Key Diseases (#BE2015716), the Priority Academic Program Development of Jiangsu Higher Education Institutions (#JX10231802), and Jiangsu Postgraduate Scientific Research and Innovation Projects (#KYZZ15_0265).

Compliance with ethical standards

This study protocol was approved by the ethical committee of the First Affiliated Hospital of Nanjing Medical University (Nanjing, China), and informed consent was obtained from all patients before the study was initialed.

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Jin Yan
    • 1
    • 2
  • Yini Dang
    • 1
    • 2
  • Shiyu Liu
    • 1
    • 2
    • 3
  • Yifeng Zhang
    • 1
    • 2
  • Guoxin Zhang
    • 1
    • 2
  1. 1.Department of GastroenterologyThe First Affiliated Hospital with Nanjing Medical UniversityNanjingChina
  2. 2.The First Clinical Medical CollegeNanjing Medical UniversityNanjingChina
  3. 3.Department of GastroenterologyThe No. 1 People’s Hospital of XuzhouXuzhouChina

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