|Table of Contents|

Study on the mechanism of lncRNA CASC11 regulating PI3K/AKT pathway through EZH2 to promote the cisplatin resistance in esophageal squamous cell carcinoma cells

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

Issue:
2023 14
Page:
2624-2631
Research Field:
Publishing date:

Info

Title:
Study on the mechanism of lncRNA CASC11 regulating PI3K/AKT pathway through EZH2 to promote the cisplatin resistance in esophageal squamous cell carcinoma cells
Author(s):
WANG Wei1; HE Tianle2; LI Yang3; YANG Suqing1
1.Department of Thoracic Surgery,the First Hospital of Handan City,Hebei Handan 056000,China;2.Naval Medical University of PLA,Shanghai 200433,China;3.Department of Sensory Control,the Second Hospital of Hebei Medical University,Hebei Shijiazhuang 050000,China.
Keywords:
long non-coding RNA CASC11; enhancer of zeste homolog 2; phosphatidylinositol-3-kinase; protein kinase B; cisplatin resistance
PACS:
R735.1
DOI:
10.3969/j.issn.1672-4992.2023.14.010
Abstract:
Objective:To investigate the regulation of lncRNA CASC11 on the EZH2 and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) signal axis,and its influence on the resistance of esophageal squamous cell carcinoma (ESCC) cells to cisplatin (DDP).Methods:ESCC tissue (76 cases) and adjacent tissue (76 cases) were taken.The normal esophageal mucosal epithelial cells (HET-1a) and ESCC cell lines (TE-1,Eca109,KYSE150,KYSE450 and KYSE510) were cultured in vitro,and the expression of lncRNA CASC11 was detected by qRT-PCR.DDP resistant ESCC cells (TE-1/DDP) were constructed by gradually increasing DDP concentration,and randomly divided into si-NC group,si-lncRNA CASC11 group,si-lncRNA CASC11+IGF-1 group,and si-lncRNA CASC11+si-PTEN group,and normal cultured TE-1 cells were also taken as Control group.Cell proliferation,drug resistance,apoptosis and migration were detected by clonal formation assay,CCK-8,flow cytometry and Transwell,respectively.qRT-PCR and Western Blot method were used to detect the expression of lncRNA CASC11 and EZH2,PI3K/AKT pathway inhibitor PTEN,PI3K/AKT pathway proteins,EMT marker proteins (E-cadherin,N-cadherin).RNA immunoprecipitation (RIP) method was used to detect the regulatory relationship of PTEN to EZH2.Chromatin immunoprecipitation (ChIP) was used to detect the regulatory relationship among EZH2,PTEN,and lncRNA CASC11.TE-1/DDP cells knocked down by lncRNA CASC11 were inoculated subcutaneously in nude mice.The tumor volume and tumor weight were detected after DDP intervention,and Ki67 activity was analyzed by immunohistochemistry.Results:The expression of lncRNA CASC11 was significantly increased in ESCC cancer tissues,ESCC cancer cell lines and TE-1/DDP cells (P＜0.05).Knockdown of lncRNA CASC11 was able to inhibit cancer cell proliferation,migration,and EMT process,trigger cell apoptosis,and inhibit cell resistance and the activation of EZH2-PI3K/AKT survival pathway (P＜0.05).The nude mouse tumor-bearing test confirmed that knockdown of lncRNA CASC11 was able to increase the sensitivity of TE-1 cells to DDP (P＜0.05).EZH2 was able to bind to the PTEN promoter and reduce the expression of PTEN,while knockdown of lncRNA CASC11 was able to reduce the binding of EZH2 to the PTEN promoter region.PTEN knockdown or IGF-1 intervention was able to partially reverse the effects of lncRNA CASC11 knockdown on anti-cancer and anti-DDP resistance (P＜0.05).Conclusion:lncRNA CASC11 can interact with EZH2 to silence PTEN,activate PI3K/AKT-mediated cell survival pathways,and increase ESCC resistance to DDP.The knockdown of lncRNA CASC11 can reduce the resistance of cancer cells to DDP and enhance the sensitivity of ESCC to DDP chemotherapy.

References:

[1]ZHOU W,LIU M,LI X,et al.Correction to:Arsenic nano complex induced degradation of YAP sensitized ESCC cancer cells to radiation and chemotherapy［J］.Cell Biosci,2021,11(1):22-36.
[2]WATERS JK,REZNIK SI.Update on management of squamous cell esophageal cancer［J］.Curr Oncol Rep,2022,24(3):375-385.
[3]CHENG J,ZHANG R,YAN M,et al.Circular RNA hsa_circ_0000277 promotes tumor progression and DDP resistance in esophageal squamous cell carcinoma［J］.BMC Cancer,2022,22(1):238.
[4]DUAN R,DU W,GUO W,et al.EZH2:a novel target for cancer treatment［J］.J Hematol Oncol,2020,13(1):104-112.
[5]PAPPAS K,MARTIN TC,WOLFE AL,et al.NOTCH and EZH2 collaborate to repress PTEN expression in breast cancer［J］.Commun Biol,2021,4(1):312-326.
[6]GAO X,QIN T,MAO J,et al.PTENP1/miR-20a/PTEN axis contributes to breast cancer progression by regulating PTEN via PI3K/AKT pathway［J］.J Exp Clin Cancer Res,2019,38(1):256-262.
[7] WANG L,LIN N,LI Y,et al.The PI3K/AKT signaling pathway regulates ABCG2 expression and confers resistance to chemotherapy in human multiple myeloma［J］.Oncol Rep,2019,41(3):1678-1690.
[8]OUYANG J,ZHONG Y,ZHANG Y,et al.Long non-coding RNAs are involved in alternative splicing and promote cancer progression［J］.Br J Cancer,2022,126(8):1113-1124.
[9]SUN X,XIN S,ZHANG Y,et al.Long non-coding RNA CASC11 interacts with YBX1 to promote prostate cancer progression by suppressing the p53 pathway［J］.Int J Oncol,2022,61(3):110.
[10]WANG B,XU W,HU C,et al.Critical roles of the lncRNA CASC11 in tumor progression and cancer metastasis:The biomarker and therapeutic target potential［J］.Genes Dis,2020,9(2):325-333.
[11]陈龙奇.制订2009第7版食管癌TNM分期标准［J］.中国胸心血管外科临床杂志,2008,15(1):52-55. CHEN LQ.Defining AJCC/UICC esophageal cancer TNM staging 7th edition (2009)［J］.Chin J Clin Thorac Cardiov Surg,2008,15(1):52-55.
[12]LIU H,ZHANG J,LUO X,et al.Overexpression of the long noncoding RNA FOXD2-AS1 promotes cisplatin resistance in esophageal squamous cell carcinoma through the miR-195/Akt/mTOR axis［J］.Oncol Res,2020,28(1):65-73.
[13]LI H,KONG R,WAN B,et al.Initiation of PI3K/AKT pathway by IGF-1 decreases spinal cord injury-induced endothelial apoptosis and microvascular damage［J］.Life Sci,2020,263(1):1185-1192.
[14]CAO Y,XIE X,LI M,et al.CircHIPK2 contributes to DDP resistance and malignant behaviors of DDP-resistant ovarian cancer cells both in vitro and in vivo through circHIPK2/miR-338-3p/CHTOP ceRNA pathway［J］.Onco Targets Ther,2021,14(1):3151-3165.
[15]SCHULPEN M,PEETERS PH,VAN DEN BRANDT PA,et al.Mediterranean diet adherence and risk of esophageal and gastric cancer subtypes in the Netherlands Cohort Study［J］.Gastric Cancer,2019,22(4):663-674.
[16]WANG X,LIU Y,LENG X,et al.UBE2T contributes to the prognosis of esophageal squamous cell carcinoma［J］.Pathol Oncol Res,2021,9(27):6325-6331.
[17]LUO Y,HUANG S,WEI J,et al.Long noncoding RNA LINC01606 protects colon cancer cells from ferroptotic cell death and promotes stemness by SCD1-Wnt/β-catenin-TFE3 feedback loop signalling［J］.Clin Transl Med,2022,12(4):e752.
[18]WONG LS,WEI L,WANG G,et al.In vivo genome-wide CRISPR activation screening identifies functionally important long noncoding RNAs in hepatocellular carcinoma［J］.Cell Mol Gastroenterol Hepatol,2022,14(5):1053-1076.
[19]杜伟,郭丽娜,庞席宁,等.LncRNA CASC11在非小细胞肺癌组织中的表达及其临床意义［J］.齐齐哈尔医学院学报,2020,41(7):815-818. DU W,GUO LN,PANG XN,et al.Expression of long non-coding RNA CASC11 in non-small cell lung cancer tissues and its clinical significance［J］.J Qiqihar Univ Med,2020,41(7):815-818.
[20]CHEN SG,WANG CH,HE RQ,et al.LncRNA CASC11 promotes the development of esophageal carcinoma by regulating KLF6［J］.Eur Rev Med Pharmacol Sci,2019,23(20):8878-8887.
[21]王运,翟展艺,赵冲,等.Zeste基因同源蛋白2对非小细胞肺癌吉西他滨耐药性的影响［J］.中华实验外科杂志,2020,37(8):1481-1484. WANG Y,ZHAI ZY,ZHAO C,et al.Effect of enhancer of zeste homolog 2 on gemcitabine resistance in non-small cell lung cancer［J］.Chin J Exp Surg,2020,37(8):1481-1484.
[22]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.
[23]LI Z,LI M,WANG D,et al.Post-translational modifications of EZH2 in cancer［J］.Cell Biosci,2020,10(1):143-156.
[24]WANG L,BO X,YI X,et al.Exosome-transferred LINC01559 promotes the progression of gastric cancer via PI3K/AKT signaling pathway［J］.Cell Death Dis,2020,11(9):723.

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2022年度河北省医学科学研究课题计划（编号：20220981）
Last Update: 1900-01-01