|Table of Contents|

Potential mechanism for the resistance of non-small cell lung cancer PC-9 cells to erlotinib analyzed through RNA sequencing

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

Issue:
2022 01
Page:
33-38
Research Field:
Publishing date:

Info

Title:
Potential mechanism for the resistance of non-small cell lung cancer PC-9 cells to erlotinib analyzed through RNA sequencing
Author(s):
LI Fanni1JIN Fanqi1ZHANG Haowei12SHE Junjun2SUN Qi2
1.Department of Talent Highland;2.Department of General Surgery,the First Affiliated Hospital of Xi'an Jiaotong University,Shaanxi Xi'an 710061,China.
Keywords:
non-small cell lung cancerRNA sequencingerlotinibdrug resistance
PACS:
R734.2
DOI:
10.3969/j.issn.1672-4992.2022.01.007
Abstract:
Objective:To analyze and compare the gene expression profiles of parental PC-9 cells and acquired erlotinib-resistant PC-9(PC-9/ER) cells through RNA sequencing,and to reveal the potential mechanism of epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI) resistance for non-small cell lung cancer(NSCLC).Methods:Intermittent exposure to erlotinib was used to establish erlotinib-resistant cell line PC-9/ER,which was validated by the curve of erlotinib concentration-cell survival rate.The differentially expressed genes of PC-9/ER cells were analyzed with GO and KEGG functional enrichment analysis.Furthermore,qRT-PCR assay was subsequently utilized to screen potential genes or possible targets participated in EGFR-TKI resistance.Results: The inhibitory effect of erlobinib on PC-9/ER cells was much less than on PC-9 cells,with the resistance index of PC-9/ER cells to erlotinib being 41.92 based on the drug concentration-cell survival rate curve.A total of 1 028 differentially expressed genes were determined in PC-9/ER cells compared with PC-9 cells,with 720 genes up-regulated and 308 genes down-regulated,which were significantly enriched in PI3K-AKT signaling pathway and pathways in cancer.The qRT-PCR verification demonstrated that the transcriptional levels of differentially expressed genes were basically consistent with the sequencing results.Conclusion:Genes including ST6GALNAC3,CYP1A1,PAPPA2,INHBE and ACSS3 might be involved in the resistance to EGFR-TKI.Follow-up experiments for the differentially express genes may provide further experimental and theoretical basis to improve the target therapy for NSCLC.

References:

[1] SIEGEL RL,MILLER KD,FUCHS HE,et al.Cancer statistics,2021[J].CA Cancer J Clin,2021,71(1):7-33.
[2] GHAFOOR Q,BAIJAL S,TANIERE P,et al.Epidermal growth factor receptor(EGFR) kinase inhibitors and non-small cell lung cancer(NSCLC)-advances in molecular diagnostic techniques to facilitate targeted therapy[J].Pathol Oncol Res,2018,24(4):723-731.
[3] WESTOVER D,ZUGAZAGOITIA J,CHO BC,et al.Mechanisms of acquired resistance to first-and second-generation EGFR tyrosine kinase inhibitors[J].Ann Oncol,2018,29(suppl 1):i10-i19.
[4] YAMAOKA T,OHBA M,MATSUNAGA Y,et al.Establishment and characterization of three afatinib-resistant lung adenocarcinoma PC-9 cell lines developed with increasing doses of afatinib[J].J Vis Exp,2019,14(148):e59473.
[5] 夏露花,宗平,王新华,等.EGFR、VEGF和nm23在非小细胞肺癌中的表达及临床意义[J].实用临床医学,2019,20(5):6-9. XIA LH,ZONG P,WANG XH,et al.Expression and clinical significance of EGFR,VEGF and nm23 in non-small-cell lung cancer[J].Practical Clinical Medicine,2019,20(5):6-9.
[6] LIU X,JIANG T,LI X,et al.Exosomes transmit T790M mutation-induced resistance in EGFR-mutant NSCLC by activating PI3K/AKT signalling pathway[J].J Cell Mol Med,2020,24(2):1529-1540.
[7] ZHOU X,WANG X,ZHU H,et al.PI3K inhibition sensitizes EGFR wild-type NSCLC cell lines to erlotinib chemotherapy[J].Exp Ther Med,2021,21(1):9.
[8] BECKER JH,GAO Y,SOUCHERAY M,et al.CXCR7 reactivates ERK signaling to promote resistance to EGFR kinase inhibitors in NSCLC[J].Cancer Res,2019,79(17):4439-4452.
[9] SATO H,YAMAMOTO H,SAKAGUCHI M,et al.Combined inhibition of MEK and PI3K pathways overcomes acquired resistance to EGFR-TKIs in non-small cell lung cancer[J].Cancer Sci,2018,109(10):3183-3196.
[10] WANG Y,LI Z,HU G,et al.Unique molecular patterns uncovered in Kawasaki disease patients with elevated serum gamma glutamyl transferase levels:implications for intravenous immunoglobulin responsiveness[J].PLoS One,2016,11(12):e0167434.
[11] HJORTEBJERG R,ESPELUND U,RASMUSSEN TR,et al.Pregnancy-associated plasma protein-A2 is associated with mortality in patients with lung cancer[J/OL].Front Endocrinol(Lausanne),2020,11:614[2020-09-02].https://www.frontiersin.org/articles/10.3389/fendo.2020.00614/full.DOI:10.3389/fendo.2020.00614.
[12] 高峰,陈丽霞,常福厚,等.CYP1A1、CYP1B1、VEGF、CAⅨ基因与肺癌关系的研究进展[J].中国生化药物杂志,2014,34(2):151-152,156. GAO F,CHEN LX,CHANG FH,et al.Research on the relationship between lung cancer with CYP1A1,CYP1B1,VEGF,CAⅨ genes[J].Chinese Journal of Biochemical Pharmaceutics,2014,34(2):151-152,156.
[13] PAN J,HUANG G,YIN Z,et al.Circular RNA FLNA acts as a sponge of miR-486-3p in promoting lung cancer progression via regulating XRCC1 and CYP1A1[J/OL].Cancer Gene Ther,2021[2021-01-26].https://www.nature.com/articles/s41417-021-00293-w.DOI:10.1038/s41417-021-00293-w.
[14] LIU J,WANG S,WANG C,et al.Prognostic value of using glucosylceramide synthase and cytochrome P450 family 1 subfamily A1 expression levels for patients with triple-negative breast cancer following neoadjuvant chemotherapy[J].Exp Ther Med,2021,21(3):247.
[15] LI L,CHEN X,HAO L,et al.Exploration of immune-related genes in high and low tumor mutation burden groups of chromophobe renal cell carcinoma[J].Biosci Rep,2020,40(7):BSR20201491.
[16] SUGIYAMA M,KIKUCHI A,MISU H,et al.Inhibin betaE(INHBE) is a possible insulin resistance-associated hepatokine identified by comprehensive gene expression analysis in human liver biopsy samples[J].PLoS One,2018,13(3):e0194798.
[17] CHANG WC,CHENG WC,CHENG BH,et al.Mitochondrial acetyl-CoA synthetase 3 is biosignature of gastric cancer progression[J].Cancer Med,2018,7(4):1240-1252.
[18] ZHANG J,DUAN H,FENG Z,et al.Acetyl-CoA synthetase 3 promotes bladder cancer cell growth under metabolic stress[J].Oncogenesis,2020,9(5):46.
[19] ZHOU L,SONG Z,HU J,et al.ACSS3 represses prostate cancer progression through downregulating lipid droplet-associated protein PLIN3[J].Theranostics,2021,11(2):841-860.

Memo

Memo:
National Natural Science Foundation of China(No.81803026);国家自然科学基金(编号:81803026);陕西省重点研发计划(编号:2019KW-067)
Last Update: 2021-12-02