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 enhances 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.