长链非编码RNA SATB2-AS1抑制肺腺癌进展的机制研究

乔勃伟; 张勇; 李明涛; 李岩

doi:10.11659/jjssx.07E023089

您当前的位置：

首页 >

文章列表页 >

长链非编码RNA SATB2-AS1抑制肺腺癌进展的机制研究

基础研究 | 更新时间：2024-10-22

- 长链非编码RNA SATB2-AS1抑制肺腺癌进展的机制研究
- Mechanism of long non-coding RNA SATB2-AS1 inhibiting progression of lung adenocarcinoma
- 局解手术学杂志 2024年33卷第10期页码：876-881
- 作者机构：
  
  空军军医大学第二附属医院胸外科，陕西西安 710038
- 作者简介：
  
  张勇，E-mail：514405743@qq.com
- 基金信息：
  
  陕西省自然科学基础研究计划项目(2020JQ-920)
- DOI：10.11659/jjssx.07E023089
  中图分类号： R394.2;R734.2
- 纸质出版日期：2024-10-25，
  
  收稿日期：2023-07-21，
- 稿件说明：
移动端阅览
乔勃伟,张勇,李明涛等.长链非编码RNA SATB2-AS1抑制肺腺癌进展的机制研究[J].局解手术学杂志,2024,33(10):876-881.

QIAO Bo-wei,ZHANG Yong,LI Ming-tao,et al.Mechanism of long non-coding RNA SATB2-AS1 inhibiting progression of lung adenocarcinoma[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2024,33(10):876-881.
乔勃伟,张勇,李明涛等.长链非编码RNA SATB2-AS1抑制肺腺癌进展的机制研究[J].局解手术学杂志,2024,33(10):876-881. DOI： 10.11659/jjssx.07E023089.

QIAO Bo-wei,ZHANG Yong,LI Ming-tao,et al.Mechanism of long non-coding RNA SATB2-AS1 inhibiting progression of lung adenocarcinoma[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2024,33(10):876-881. DOI： 10.11659/jjssx.07E023089.

摘要

目的

长链非编码RNA (lncRNA) SATB2的反义转录物（SATB2-AS1）对肺腺癌细胞生物学功能的影响和机制研究。

方法

收集25例肺腺癌患者的肿瘤组织和癌旁组织，检测SATB2-AS1表达水平。用lncRNA SATB2-AS1的过表达载体（pcDNA-SATB2-AS1）和shRNA或IGF2BP2的shRNA（sh-SATB2-AS1；sh-IGF2BP2）和/或SLC7A11的shRNA（sh-SLC7A11）转染肺腺癌细胞A549。RIP分析评估IGF2BP2蛋白分别与SATB2-AS1或SLC7A11 mRNA的结合；CCK-8和Transwell实验分别用于检测肺腺癌细胞的增殖和侵袭能力；RT-qPCR和Western blot分别检测基因和蛋白表达。

结果

与癌旁组织和人正常支气管上皮细胞系BEAS-2B相比，SATB2-AS1在肺腺癌患者的肿瘤组织和肺腺癌细胞系中的表达显著下调（

0.01）。过表达SATB2-AS1抑制A549细胞增殖和侵袭，沉默SATB2-AS1促进细胞增殖和侵袭（

0.05）。过表达SATB2-AS1后A549细胞中的Fe

浓度、活性氧（ROS）水平以及丙二醛（MDA）含量显著降低（

0.01），还原性谷胱甘肽（GSH）含量及铁死亡关键蛋白SLC7A11、GPX4的表达显著升高（

0.01）。SATB2-AS1通过与IGF2BP2蛋白结合显著促进IGF2BP2蛋白与SLC7A11 mRNA结合，降低SLC7A11 mRNA的稳定性（

0.01）。沉默SLC7A11显著逆转了SATB2-AS1沉默对A549细胞的影响。

结论

lncRNA SATB2-AS1通过招募IGF2BP2蛋白破坏SLC7A11 mRNA稳定性，诱导肺腺癌细胞铁死亡，抑制细胞增殖和侵袭，从而抑制肺腺癌进展。

Abstract

Objective

To investigate the effect of long non-coding RNA（lncRNA） antisense transcript of SATB2 protein （SATB2-AS1） on the biological function of lung adenocarcinoma cells and its mechanism.

Methods

Tumor tissues and adjacent tissues from 25 patients with lung adenocarcinoma were collected to detect the expression of SATB2-AS1. Then，the overexpression vector of lncRNA SATB2-AS1 （pcDNA-SATB2-AS1） and shRNA or shRNA of IGF2BP2 （sh-SATB2-AS1；sh-IGF2BP2） and/or shRNA of SLC7A11 （sh-SLC7A11） were transfected into lung adenocarcinoma cell A549.RIP assay was used to estimate the binding of IGF2BP2 protein to SATB2-AS1 or SLC7A11 mRNA，respectively；CCK-8 and Transwell assay were used to detect the proliferation and invasion ability of lung adenocarcinoma cells；RT-qPCR and Western blot assay were used to detect gene expression and protein expression， respectively.

Results

Compared with adjacent tissues and human bronchial epithelial cell BEAS-2B，the expression of SATB2-AS1 was significantly down-regulated in tumor tissues of patients with lung adenocarcinoma and lung adenocarcinoma cells （

0.01）. Overexpression of SATB2-AS1 significantly inhibited the proliferation and invasion of A549 cells， while silencing SATB2-AS1 significantly promoted the cell proliferation and invasion （

0.05）. Moreover， overexpression of SATB2-AS1 significantly reduced Fe

concentration， reactive oxygen species（ROS） level， and malondialdehyde （MDA） content in A549 cells（

0.01）， and increased glutathione （GSH） content， the expression of SLC7A11 and GPX4 which were the key proteins of ferroptosis （

0.01）. Meanwhile， SATB2-AS1 significantly promoted IGF2BP2 protein binding to SLC7A11 mRNA by binding to IGF2BP2 protein， and reduced the stability of SLC7A11 mRNA （

0.01）. Silencing SLC7A11 significantly reversed the effects of silencing SATB2-AS1 on A549 cells.

Conclusion

LncRNA SATB2-AS1 destabilizes SLC7A11 mRNA by recruiting IGF2BP2 protein， induces the ferroptosis of lung adenocarcinoma cells， inhibits the cell proliferation and invasion， and thus inhibits the progression of lung adenocarcinoma.

关键词

肺腺癌lncRNA SATB2-AS1IGF2BP2SLC7A11铁死亡

Keywords

lung adenocarcinomalncRNA SATB2-AS1IGF2BP2SLC7A11ferroptosis

references

Ciccone G，Ibba ML，Coppola G，et al. The small RNA landscape in NSCLC：current therapeutic applications and progresses［J］. Int J Mol Sci，2023，24（7）：6121.doi：10.3390/ijms24076121http://dx.doi.org/10.3390/ijms24076121.

Seguin L，Durandy M，Feral CC. Lung adenocarcinoma tumor origin：a guide for personalized medicine［J］. Cancers，2022，14（7）：1759.doi：10.3390/cancers14071759http://dx.doi.org/10.3390/cancers14071759.

Lee E，Kazerooni EA. Lung cancer screening［J］.Semin Respir Crit Care Med，2022，43（6）：839-850. doi：10.1055/s-0042-1757885http://dx.doi.org/10.1055/s-0042-1757885.

Petty WJ，Paz-ares L. Emerging strategies for the treatment of small cell lung cancer：a review［J］. JAMA Oncol，2023，9（3）：419-29. doi：10.1001/jamaoncol.2022.5631http://dx.doi.org/10.1001/jamaoncol.2022.5631.

Bridges MC，Daulagala AC，Kourtidis A. LNCcation：lncRNA localization and function［J］. J Cell Biol，2021，220（2）：e202009045. doi：10.1083/jcb.202009045http://dx.doi.org/10.1083/jcb.202009045.

Herman AB，Tsitsipatis D，Gorospe M. Integrated lncRNA function upon genomic and epigenomic regulation［J］. Mol Cell，2022，82（12）：2252-2266. doi：10.1016/j.molcel.2022.05.027http://dx.doi.org/10.1016/j.molcel.2022.05.027.

Cheng S，Xia B，Li H，et al. Long non-coding RNA SATB2-AS1 inhibits microRNA-155-3p to suppress breast cancer cell growth by promoting breast cancer metastasis suppressor 1-like［J］. Cancer Cell Int，2020，20：321. doi：10.1186/s12935-020-01411-8http://dx.doi.org/10.1186/s12935-020-01411-8.

Huang J，Yang Y，Zhao F，et al. LncRNA SATB2-AS1 overexpression represses the development of hepatocellular carcinoma through regulating the miR-3678-3p/GRIM-19 axis［J］. Cancer Cell Int，2023，23（1）：82. doi：10.1186/s12935-023-02901-1http://dx.doi.org/10.1186/s12935-023-02901-1.

Wang YQ，Jiang DM，Hu SS，et al. SATB2-AS1 suppresses colorectal carcinoma aggressiveness by inhibiting SATB2-dependent snail transcription and epithelial-mesenchymal transition［J］. Cancer Res，2019，79（14）：3542-3556. doi：10.1158/0008-5472.Can-18-2900http://dx.doi.org/10.1158/0008-5472.Can-18-2900.

Xu M，Xu X，Pan B，et al. LncRNA SATB2-AS1 inhibits tumor metastasis and affects the tumor immune cell microenvironment in colorectal cancer by regulating SATB2［J］. Mol Cancer，2019，18（1）：135. doi：10.1186/s12943-019-1063-6http://dx.doi.org/10.1186/s12943-019-1063-6.

Lu L，Liu LP，Zhao QQ，et al. Identification of a ferroptosis-related lncRNA signature as a novel prognosis model for lung adenocarcinoma ［J］. Front Oncol，2021，11：675545.doi：10.3389/fonc. 2021. 675545http://dx.doi.org/10.3389/fonc.2021.675545.

Wang J，Chen L，Qiang P. The role of IGF2BP2，an m6A reader gene，in human metabolic diseases and cancers［J］. Cancer Cell Int，2021，21（1）：99. doi：10.1186/s12935-021-01799-xhttp://dx.doi.org/10.1186/s12935-021-01799-x.

Mao J，Qiu H，Guo L. LncRNA HCG11 mediated by METTL14 inhibits the growth of lung adenocarcinoma via IGF2BP2/LATS1［J］. Biochem Biophys Res Commun，2021，580：74-80. doi：10.1016/j.bbrc.2021.09.083http://dx.doi.org/10.1016/j.bbrc.2021.09.083.

Pan X，Huang B，Ma Q，et al. Circular RNA circ-TNPO3 inhibits clear cell renal cell carcinoma metastasis by binding to IGF2BP2 and destabilizing SERPINH1 mRNA［J］. Clin Translat Med，2022，12（7）：e994. doi：10.1002/ctm2.994http://dx.doi.org/10.1002/ctm2.994.

Jia M，Shi Y，Xie Y，et al. WT1-AS/IGF2BP2 Axis is a potential diagnostic and prognostic biomarker for lung adenocarcinoma according to ceRNA network comprehensive analysis combined with experiments［J］. Cells，2021，11（1）：25. doi：10.3390/cells11010025http://dx.doi.org/10.3390/cells11010025.

Qu L，He X，Tang Q，et al. Iron metabolism，ferroptosis，and lncRNA in cancer：knowns and unknowns［J］. J Zhejiang Univ Sci B，2022，23（10）：844-862. doi：10.1631/jzus.B2200194http://dx.doi.org/10.1631/jzus.B2200194.

Zuo YB，Zhang YF，Zhang R，et al. Ferroptosis in cancer progression：role of noncoding RNAs ［J］. Int J Biol Sci，2022，18（5）：1829-1843. doi：10.7150/ijbs.66917http://dx.doi.org/10.7150/ijbs.66917.

Mou Y，Wang J，Wu J，et al. Ferroptosis，a new form of cell death：opportunities and challenges in cancer ［J］. J Hematol Oncol，2019，12（1）：34. doi：10.1186/s13045-019-0720-yhttp://dx.doi.org/10.1186/s13045-019-0720-y.

Chen X，Yu C，Kang R，et al. Cellular degradation systems in ferroptosis ［J］. Cell Death Differ，2021，28（4）：1135-1148. doi：10.1038/s41418-020-00728-1http://dx.doi.org/10.1038/s41418-020-00728-1.

Liu J，Kang R，Tang D. Signaling pathways and defense mechanisms of ferroptosis ［J］. FEBS J，2022，289（22）：7038-7050. doi：10.1111/febs.16059http://dx.doi.org/10.1111/febs.16059.

Koppula P，Zhuang L，Gan B. Cystine transporter SLC7A11/xCT in cancer：ferroptosis，nutrient dependency，and cancer therapy ［J］. Protein Cell，2021，12（8）：599-620. doi：10.1007/s13238-020-00789-5http://dx.doi.org/10.1007/s13238-020-00789-5.

Yang J，Zhou Y，Xie S，et al. Metformin induces Ferroptosis by inhibiting UFMylation of SLC7A11 in breast cancer ［J］. J Exp Clin Cancer Res，2021，40（1）：206. doi：10.1186/s13046-021-02012-7http://dx.doi.org/10.1186/s13046-021-02012-7.

Lin W，Wang C，Liu G，et al. SLC7A11/xCT in cancer：biological functions and therapeutic implications ［J］. Am J Cancer Res，2020，10（10）：3106-3126.

浏览量

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

FOXM1上调ELK1介导铁死亡促进宫颈癌细胞顺铂耐药性

抗氧化干预对低氧低糖诱导血管平滑肌细胞自噬和铁死亡的影响

右美托咪啶减轻急性肺损伤的机制研究