HOTAIR Competitively Binds MiRNA330 as a Molecular Sponge to Increase the Resistance of Gastric Cancer to Trastuzumab
| Autor: | Sai-Qi Wang, Xiaobing Chen, Liangyu Bie, Suxia Luo, Ping Guo, Xiao-Yu Lu, Yan Wei, Yu Mu, Dan Li |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research Cell Survival Receptor ErbB-2 Afatinib Mice Nude Biology Transfection Viral vector Mice 03 medical and health sciences Antineoplastic Agents Immunological 0302 clinical medicine Stomach Neoplasms Trastuzumab Cell Line Tumor Drug Discovery medicine Animals Humans ERBB4 Cell Proliferation Pharmacology Mice Inbred BALB C Cancer HOTAIR medicine.disease Xenograft Model Antitumor Assays Tumor Burden MicroRNAs Treatment Outcome 030104 developmental biology Oncology Drug Resistance Neoplasm Cell culture 030220 oncology & carcinogenesis Cancer cell Cancer research Female RNA Long Noncoding Signal Transduction medicine.drug |
| Zdroj: | Current Cancer Drug Targets. 20:700-709 |
| ISSN: | 1568-0096 |
| DOI: | 10.2174/1568009620666200504114000 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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