机构：[1]Department of Gynecology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Center, Kunming 650118, China.[2]Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Center, No. 519 Kunzhou Road, Kunming 650118, Yunnan, China.[3]Department of Nuclear Medicine, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Center, Kunming 650118, China.[4]Cancer Research Institute, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Center, Kunming 650118, China.
Gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, has been used as first-line treatment for advanced non-small-cell lung cancer (NSCLC). However, during treatment, cancer cells often develop resistance to gefitinib, the mechanisms of which are not fully understood. This study was designed to elucidate the expression and role of long non-coding RNA (lncRNA)-PCAT-1, a potential biomarker for drug resistance and a therapeutic target for NSCLC, in gefitinib resistance in NSCLC cells.In this study, we verified differential PCAT-1 expression in NSCLC gefitinib-resistant tissues or cells. PCAT-1 knockdown, clone formation, Transwell, flow cytometry, and immunofluorescence assays were used to verify the correlation between PCAT-1 and gefitinib sensitivity. A nude mouse tumor-bearing model verified that PCAT-1 can reverse gefitinib resistance in vivo. Then, a PI3K/Akt agonist was used to verify the possible mechanism of PCAT-1 action.PCAT-1 is highly expressed in gefitinib-resistant NSCLC tissues and cells. PCAT-1 knockdown enhanced gefitinib sensitivity and gefitinib-induced apoptosis in H1299/GR cells. PCAT-1 knockdown reduced tumor volume and weight, and reversed acquired gefitinib resistance in vivo. PCAT-1 knockdown inhibited AKT and GSK3 phosphorylation in H1299/GR cells. A PI3K/AKT agonist reversed PCAT-1 knockdown-mediated enhancement of gefitinib sensitivity in H1299/GR cells CONCLUSION: PCAT-1 knockdown improves sensitivity to gefitinib by inhibition of AKT and GSK3 phosphorylation in NSCLC. PCAT-1 is as potential target for improving the clinical efficacy of gefitinib.
基金：
This study was supported by the Regional Program of the National Natural Science
Foundation of China (No. 81760423), the Youth Program of the National
Natural Science Foundation of China (No. 81902652), the Basic research in
Yunnan Province (Kunming Medical University Joint Project): 2019FE001(-150),
2018FE001(-247), the Natural Science Foundation, Regional Science Foundation
Project (No. 81960322), the National Natural Science Foundation of China
(No. 81560380), the Project of Medical and Health Technology Development
Program of Yunnan Province (No. 2017NS203), and the Academic Leaders
Training Program of Yunnan Provincial Health and Family Planning Commission
(No. D-201601).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2021]版：
大类|2 区医学
小类|3 区呼吸系统
最新[2023]版：
大类|2 区医学
小类|2 区呼吸系统
第一作者：
第一作者机构：[1]Department of Gynecology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Center, Kunming 650118, China.
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Wang Shaojia,Liu Chao,Lei Qing,et al.Relationship between long non-coding RNA PCAT-1 expression and gefitinib resistance in non-small-cell lung cancer cells[J].Respiratory research.2021,22(1):146.doi:10.1186/s12931-021-01719-7.
APA：
Wang Shaojia,Liu Chao,Lei Qing,Wu Zhengwei,Miao Xiangshuai...&Wang Weiwei.(2021).Relationship between long non-coding RNA PCAT-1 expression and gefitinib resistance in non-small-cell lung cancer cells.Respiratory research,22,(1)
MLA：
Wang Shaojia,et al."Relationship between long non-coding RNA PCAT-1 expression and gefitinib resistance in non-small-cell lung cancer cells".Respiratory research 22..1(2021):146
