|Table of Contents|

Study on the mechanism of LINC01426 regulating cisplatin resistance in non-small cell lung cancer through EZH2

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

Issue:
2023 14
Page:
2605-2613
Research Field:
Publishing date:

Info

Title:
Study on the mechanism of LINC01426 regulating cisplatin resistance in non-small cell lung cancer through EZH2
Author(s):
CHEN Yunfeng; CUI Wenjie; SHI Hai; LIU Xiangqun
Department of Respiratory and Critical Care Medicine，Xuzhou First People's Hospital，Jiangsu Xuzhou 221116，China.
Keywords:
non-small cell lung cancer; LINC01426; cisplatin resistance; enhancer of zeste homolog 2; PTEN
PACS:
R734.2
DOI:
10.3969/j.issn.1672-4992.2023.14.008
Abstract:
Objective:To investigate the effect of long non-coding RNA (lncRNA) LINC01426 on cisplatin (DDP) resistance in non-small cell lung cancer (NSCLC) and its potential mechanism.Methods:A549 cells and anti-DDP cell line A549/DDP were cultured in vitro.The reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to detect the mRNA expressions of LINC01426 and enhancer of zeste homolog 2 (EZH2) in cells.The interaction between LINC01426 and EZH2 was validated by RNA-protein interaction prediction (RIP-seq),RNA immunoprecipitation (RIP),RT-qPCR and chromatin immunoprecipitation (ChIP) assays.A549/DDP cells were grouped into Control group,si-NC group,si-LINC01426 group,si-LINC01426+pc-NC group,and si-LINC01426+pc-EZH2 group,and were transfected and cultured for 48 h.RT-qPCR was implemented to detect LINC01426,EZH2 and PTEN mRNA expression of cells in each group.CCK-8 was implemented to detect the sensitivity of cells to DDP.Colony formation assay was used to detect cell proliferation.Flow cytometry was used to detect cell apoptosis.Western blot was performed to analyze EZH2,PTEN,AKT and p-AKT protein expression in cells.A nude mouse xenograft model was performed to verify whether LINC01426 was involved in the sensitivity of NSCLC cells to DDP in vivo.Results:The mRNA levels of LINC01426 and EZH2 in A549/DDP cells were higher than those in A549 cells.LINC01426 was mainly distributed in the nucleus and could interact with EZH2.The knockdown of LINC01426 upregulated PTEN expression,reduced p-AKT/AKT ratio,enhanced the sensitivity of A549/DDP cells to DDP,inhibited the proliferation of A549/DDP cells,and induced apoptosis (all P＜0.05).The nude mouse xenograft experiments confirmed that knockdown of LINC01426 upregulated PTEN expression,decreased p-AKT/AKT ratio,inhibited the growth of A549/DDP cells in vivo and enhanced the sensitivity of A549/DDP cells to DDP in vivo (P＜0.05).Silencing PTEN attenuated the effect of LINC01426 knockdown on DDP sensitivity of A549/DDP cells in nude mice (P＜0.05).Overexpression of EZH2 could reverse the inhibition of LINC01426 knockdown on cell proliferation and the promotion on apoptosis and DDP sensitivity (P＜0.05).Conclusion:LINC01426 is up-regulated in A549/DDP cells,and knockdown of LINC01426 may upregulate the expression of PTEN by inhibiting EZH2,thereby inhibiting the activation of PI3K/AKT pathway,inhibiting A549/DDP cell proliferation in vitro and tumor growth in vivo and enhancing the sensitivity of NSCLC cells to DDP.

References:

[1]BRODERICK SR.Adjuvant and neoadjuvant immunotherapy in non-small cell lung cancer［J］.Thorac Surg Clin,2020,30(2):215-220.
[2]MISRI S，KAUL K，MISHRA S，et al.Cannabidiol inhibits tumorigenesis in cisplatin-resistant non-small cell lung cancer via TRPV2［J］.Cancers (Basel)，2022，14(5):1181-1195.
[3]LIU X，ZHANG X，DU S.Long non-coding RNA ACTA2-AS1 inhibits the cisplatin resistance of non-small cell lung cancer cells through inhibiting autophagy by suppressing TSC2［J］.Cell Cycle，2022，21(4):368-378.
[4]CAO J，ANG Z，SU Z.Long non-coding RNA LINC01426 facilitates glioblastoma progression via sponging miR-345-3p and upregulation of VAMP8［J］.Cancer Cell Int，2020，20(1):327-335.
[5]TIAN B，HAN X，LI G，et al.A long intergenic non-coding RNA,LINC01426,promotes cancer progression via AZGP1 and predicts poor prognosis in patients with LUAD［J］.Mol Ther Methods Clin Dev，2020，18(1):765-780.
[6]DAI J，WANG B，ZHAO Y，et al.Long noncoding RNA LINC01426 sequesters microRNA-519d-5p to promote non-small cell lung cancer progression by increasing ETS1 expression［J］.Cancer Manag Res，2020，12(1):12697-12708.
[7]ZHOU W，WANG J，MAN WY，et al.siRNA silencing EZH2 reverses cisplatin-resistance of human non-small cell lung and gastric cancer cells［J］.Asian Pac J Cancer Prev，2015，16(6):2425-2430.
[8]YANG D，FENG W，ZHUANG Y，et al.Long non-coding RNA linc00665 inhibits CDKN1C expression by binding to EZH2 and affects cisplatin sensitivity of NSCLC cells［J］.Mol Ther Nucleic Acids，2021，23(1):1053-1065.
[9]SU M，XIAO Y，TANG J，et al.Role of lncRNA and EZH2 interaction/regulatory network in lung cancer［J］.J Cancer，2018，9(22):4156-4165.
[10]WANG Y，WU Y，XIE S.CircPTK2 inhibits cell cisplatin (CDDP) resistance by targeting miR-942/TRIM16 axis in non-small cell lung cancer (NSCLC)［J］.Bioengineered，2022，13(2):3651-3664.
[11]SUN X，CHEN Z.Cancer-associated fibroblast-derived CCL5 contributes to cisplatin resistance in A549 NSCLC cells partially through upregulation of lncRNA HOTAIR expression［J］.Oncol Lett，2021，22(4):696-706.
[12]GUO S，ZHANG L，ZHANG Y，et al.Long non-coding RNA TUG1 enhances chemosensitivity in non-small cell lung cancer by impairing microRNA-221-dependent PTEN inhibition［J］.Aging (Albany NY)，2019，11(18):7553-7569.
[13]TANG H，HAN X，LI M，et al.Linc00221 modulates cisplatin resistance in non-small-cell lung cancer via sponging miR-519a［J］.Biochimie，2019，162(1):134-143.
[14]TAN D，LI G，ZHANG P，et al.LncRNA SNHG12 in extracellular vesicles derived from carcinoma-associated fibroblasts promotes cisplatin resistance in non-small cell lung cancer cells［J］.Bioengineered，2022，13(1):1838-1857.
[15]ENGREITZ JM，HAINES JE，PEREZ EM，et al.Local regulation of gene expression by lncRNA promoters,transcription and splicing［J］.Nature，2016，539(7629):452-455.
[16]JONAS K，CALIN GA，PICHLER M.RNA-binding proteins as important regulators of long non-coding RNAs in cancer［J］.Int J Mol Sci，2020，21(8):2969-2990.
[17]LIU Y，HU Q，WANG X.AFAP1-AS1 induces cisplatin resistance in non-small cell lung cancer through PI3K/AKT pathway［J］.Oncol Lett，2020，19(1):1024-1030.
[18]QIU C，LI S，SUN D，et al.lncRNA PVT1 accelerates progression of non-small cell lung cancer via targeting miRNA-526b/EZH2 regulatory loop［J］.Oncol Lett，2020，19(2):1267-1272.
[19]CHEN Z，CHEN Q，CHENG Z，et al.Long non-coding RNA CASC9 promotes gefitinib resistance in NSCLC by epigenetic repression of DUSP1［J］.Cell Death Dis，2020，11(10):858.
[20]YANG D，FENG W，ZHUANG Y，et al.Long non-coding RNA linc00665 inhibits CDKN1C expression by binding to EZH2 and affects cisplatin sensitivity of NSCLC cells［J］.Mol Ther Nucleic Acids，2021，23:1053-1065.
[21]ZANG X，GU J，ZHANG J，et al.Exosome-transmitted lncRNA UFC1 promotes non-small-cell lung cancer progression by EZH2-mediated epigenetic silencing of PTEN expression［J］.Cell Death Dis，2020，11(4):215.
[22]SUN B，HU N，CONG D，et al.MicroRNA-25-3p promotes cisplatin resistance in non-small-cell lung carcinoma (NSCLC) through adjusting PTEN/PI3K/AKT route［J］.Bioengineered，2021，12(1):3219-3228.

Memo

Memo:
徐州市卫生健康委面上项目（编号：XWKYHT20210529）；徐州市第一人民医院青苗工程（编号：QMHB2021017）
Last Update: 1900-01-01