Title:HOTAIR Competitively Binds MiRNA330 as a Molecular Sponge to Increase the Resistance of Gastric Cancer to Trastuzumab
Volume: 20
Issue: 9
关键词:
曲妥珠单抗，HOTAIR，阿法替尼，ERBB4，HER2，miRNA330，胃癌。
摘要:
Background: HOTAIR, one of the most widely studied long non-coding RNAs in tumors,
is closely related to tumor proliferation, migration, invasion and chemoresistance.
Objective: Here, we studied the mechanism behind proliferation and chemoresistance processes.
Methods: A total of 75 samples were collected from patients who underwent surgical resection of
their gastric cancer and received trastuzumab treatment. Primary cells were isolated and cultured.
We also developed a cell line overexpressing HOTAIR by constructing a lentiviral vector. These cell
lines were studied using an array of established biomolecular methods.
Results: We found that HOTAIR levels were inversely associated with sensitivity to trastuzumab in
gastric cancer and that overexpression of HOTAIR can promote the proliferation and invasion of
gastric cancer cells. The sensitivity of cells overexpressing HOTAIR to two different types of human
epidermal growth factor receptor 2 (HER2) inhibitors (trastuzumab and afatinib) showed that overexpression
of HOTAIR is specific for trastuzumab resistance. Furthermore, luciferase reporter gene
assay and western blot assay showed that there is a HOTAIR-miRNA330-ERBB4 competitive endogenous
RNA regulatory network with miRNA330 as the core.
Conclusion: HOTAIR can not only promote tumor proliferation but also enhance the resistance of
tumor cells to drugs. Our experimental data not only showed strong expression of HOTAIR in gastric
cancer, but also that strong expression of HOTAIR caused the sensitivity of gastric cancer cells
to trastuzumab, which is a useful reference for postoperative medication.
