|Table of Contents|

lncRNA LUCAT1 promotes gefitinib resistance in lung adenocarcinoma PC-9/GR cells by affecting autophagy

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2024 02
Page:
255-261
Research Field:
Publishing date:

Info

Title:
lncRNA LUCAT1 promotes gefitinib resistance in lung adenocarcinoma PC-9/GR cells by affecting autophagy
Author(s):
JIANG Mei1; 2; WANG Xin1; 2; LI Lei1; 2; LI Leyao1; 2; YAO Yujun1; LI Yajun1
1.Oncology Department，the Third Affiliated Hospital of Zunyi Medical University/the First People's Hospital of Zunyi,Guizhou Zunyi 563000,China;2.Oncology Department，the Third Affiliated Hospital of Zunyi Medical University/Scientific Research Center,the First People's Hospital of Zunyi,Guizhou Zunyi 563000,China.
Keywords:
lung adenocarcinoma; lncRNA LUCAT1; autophagy; gefitinib; acquired drug resistance
PACS:
R734.2
DOI:
10.3969/j.issn.1672-4992.2024.02.009
Abstract:
Objective:To explore the effect of lncRNA LUCAT1 on drug resistance of lung adenocarcinoma PC-9/GR cells and to study its potential mechanism of drug resistance.Methods:CCK-8,colony formation and Transwell migration assay were used to detect the drug sensitivity,proliferation,clone formation and migration of cells.The mRNA expression of lncRNA LUCAT1 in cells was detected by qRT-PCR.The expression of key autophagy proteins p62,Beclin1,LC3-Ⅱ/LC3-Ⅰ was detected by Western Blot,and the number of autophagosomes in the cells was observed by transmission electron microscope.Lentiviral transfection was used to knock down lncRNA LUCAT1 and control cells (PC-9/GR-shLUCAT1,PC-9/GR-NC).After 48 h,the transfection of lentivirus was observed by fluorescence microscope.The transfection effect of knockdown LUCAT1 was further detected by qRT-PCR.The changes of drug resistance,cloning and migration ability of cells in each group before and after regulation of LUCAT1 were detected and Western Blot assay was used to detect the expression of autophagy key proteins in each group.Results:Compared with parent cells PC-9,PC-9/GR cells had stronger drug resistance,proliferation and migration ability (P＜0.05).The relative mRNA expression of lncRNA LUCAT1 in PC-9/GR cells was higher than that in parent cells (P＜0.05),and the protein expression of autophagy key gene LC3-II/LC3-I was higher,and the protein expression of p62 was lower than that in parent cells (P＜0.05),but there was no significant difference in the expression of Beclin1 protein between PC-9/GR and PC-9 cells (P＞0.05).The number of autophagosomes in PC-9/GR cells was significantly higher than that in parent cells (P＜0.05).After knocking down LUCAT1,the drug resistance,colony formation ability and migration ability of PC-9/GR cells were significantly weaker than those of the control group (P＜0.05).At the same time,the autophagy key gene LC3-II/LC3-I decreased and p62 protein increased (P＜0.05).In addition,we found that knocking down LUCAT1 in PC-9/GR cells did not affect the protein expression of Beclin1 (P＞0.05),the key gene of autophagy.LUCAT1 may not regulate autophagy by affecting Beclin1 protein in secondary drug resistant cells.Conclusion:Lung adenocarcinoma cells PC-9/GR have high expression of lncRNA LUCAT1 and high level of autophagy.LUCAT1 may promote lung adenocarcinoma cells to become resistant to gefitinib by activating autophagy by affecting LC3B/p62-mediated autophagy pathway.

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Memo

Memo:
National Natural Science Foundation of China(No.82060544）；国家自然科学基金（编号：82060544）；贵州省科技计划项目（编号：黔科合基础-ZK［2023］一般486）；遵义市第一人民医院研究与试验发展课题（编号：院科字（2020）10号）
Last Update: 1900-01-01