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Published on: February 12, 2017
Elevated HOTAIR expression associated with cisplatin resistance in non-small cell lung cancer patients
Ming-Yue Liu1, Xi-Qing Li2, Tian-Hui Gao2
1Department 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.
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.
Insights
Elevated HOTAIR long noncoding RNA expression correlates with non-small cell lung cancer drug resistance. Targeting HOTAIR may offer new therapeutic strategies for resistant lung cancer patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Investigates mechanisms of drug resistance in non-small cell lung cancer (NSCLC).
- Focuses on the role of long noncoding RNAs (lncRNAs) in NSCLC drug resistance.
- Aims to identify novel therapeutic targets to improve survival rates for drug-resistant NSCLC patients.
Purpose of the Study:
- To determine if HOTAIR lncRNA influences drug resistance in NSCLC.
- To elucidate the molecular mechanisms underlying HOTAIR-mediated drug resistance.
- To assess HOTAIR as a potential therapeutic target for drug-resistant NSCLC.
Main Methods:
- Collected NSCLC patient tissue samples for HOTAIR expression analysis.
- Utilized MTT assays and tumor sphere formation assays to assess drug sensitivity.
- Performed Western blot analysis to investigate molecular mechanisms and biomarker expression.
Main Results:
- Higher HOTAIR expression observed in drug-resistant NSCLC tissues compared to non-resistant tissues.
- Elevated HOTAIR expression conferred cisplatin resistance in NSCLC cell lines (A549/CDDP).
- Reduced HOTAIR expression increased sensitivity to cisplatin, while overexpression enhanced resistance. HOTAIR upregulation linked to tumor stem cell biomarkers and Klf4.
Conclusions:
- Elevated HOTAIR expression is significantly associated with drug resistance in NSCLC.
- HOTAIR's role in drug resistance is linked to Klf4 upregulation.
- HOTAIR presents a promising therapeutic target for overcoming drug resistance in NSCLC.
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