Ming-Yue Liu1, Xi-Qing Li2, Tian-Hui Gao2, Yao Cui2, Ning Ma2, Yun Zhou2, Guo-Jun Zhang3. 1. Department of Respiratory Medicine, First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China;; Department of Oncology, Henan Provincial People's Hospital (Zhengzhou University People's Hospital), Zhengzhou 450003, China. 2. Department of Oncology, Henan Provincial People's Hospital (Zhengzhou University People's Hospital), Zhengzhou 450003, China. 3. Department of Respiratory Medicine, First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Abstract
BACKGROUND: This study investigated the mechanism of drug resistance in non-small cell lung cancer (NSCLC) patients. We specifically studied whether long noncoding RNAs influence drug resistance in NSCLC to discover new therapeutic targets to increase the survival rate of drug-resistant NSCLC patients. METHODS: Tissue samples were collected from NSCLC patients, and total RNA was isolated for assessment of HOTAIR expression and drug resistance status. MTT assays, tumor sphere formation assays, and western blot were performed to cytologically determine the relationship between HOTAIR expression and cisplatin resistance, as well as to elucidate the potential molecular mechanism involved. RESULTS: HOTAIR expression in tissues of drug-resistant NSCLC patients was higher than that of non-drug-resistant patients. HOTAIR expression was elevated in cisplatin-resistant cell strains (A549/CDDP), and reducing HOTAIR expression increased the sensitivity of A549/CDDP cells to cisplatin. In addition, overexpression of HOTAIR in A549 cells increased resistance to cisplatin. Tumor sphere formation assays showed that the volume of spheres formed by cell strains expressing elevated levels of HOTAIR was greater than that of cell strains with low expression. Western blot experiments showed that elevated expression of HOTAIR upregulated tumor stem cell-related biomarkers and HOTAIR expression was directly related to Klf4 expression. CONCLUSIONS: Elevated HOTAIR expression is associated with drug resistance in NSCLC patients and is related to Klf4 upregulation, providing a new therapeutic target for drug-resistant NSCLC patients.
BACKGROUND: This study investigated the mechanism of drug resistance in non-small cell lung cancer (NSCLC) patients. We specifically studied whether long noncoding RNAs influence drug resistance in NSCLC to discover new therapeutic targets to increase the survival rate of drug-resistant NSCLCpatients. METHODS: Tissue samples were collected from NSCLCpatients, and total RNA was isolated for assessment of HOTAIR expression and drug resistance status. MTT assays, tumor sphere formation assays, and western blot were performed to cytologically determine the relationship between HOTAIR expression and cisplatin resistance, as well as to elucidate the potential molecular mechanism involved. RESULTS:HOTAIR expression in tissues of drug-resistant NSCLCpatients was higher than that of non-drug-resistant patients. HOTAIR expression was elevated in cisplatin-resistant cell strains (A549/CDDP), and reducing HOTAIR expression increased the sensitivity of A549/CDDP cells to cisplatin. In addition, overexpression of HOTAIR in A549 cells increased resistance to cisplatin. Tumor sphere formation assays showed that the volume of spheres formed by cell strains expressing elevated levels of HOTAIR was greater than that of cell strains with low expression. Western blot experiments showed that elevated expression of HOTAIR upregulated tumor stem cell-related biomarkers and HOTAIR expression was directly related to Klf4 expression. CONCLUSIONS: Elevated HOTAIR expression is associated with drug resistance in NSCLCpatients and is related to Klf4 upregulation, providing a new therapeutic target for drug-resistant NSCLCpatients.
Entities:
Keywords:
A549 cells; HOTAIR; Klf4; cisplatin; drug resistance; non-small cell lung cancer (NSCLC)
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