| Lin Huang,Bin Li,Zuowei Hu. AGAP2-AS1 affects TNM staging and prognosis of lung cancer patients by acting on SLC7A11 mRNA stability and ferroptosis. Oncol Transl Med, 2023, 9: 115-120. |
| LncRNA AGAP2-AS1在肺癌中通过SLC7A11激活IGF2BP2通路促进肿瘤发生和铁死亡抵抗 |
| AGAP2-AS1 affects TNM staging and prognosis of lung cancer patients by acting on SLC7A11 mRNA stability and ferroptosis |
| Received:November 25, 2022 Revised:April 18, 2023 |
| DOI：10.1007/s10330-022-0620-0 |
| 中文关键词: AGAP2-AS1; 铁死亡;肺癌; mRNA稳定性 |
| 英文关键词: AGAP2-AS1; ferroptosis; lung cancer; mRNA stability |
| 基金项目:武汉市医学科研项目立项任务书中医药类青年项目（立项编号：WZ20Q04） |
| Author Name | Affiliation | E-mail | | Lin Huang | Department of Oncology, Wuhan No.1 Hospital | 16534356@qq.com | | Bin Li | Department of Oncology, Wuhan No.1 Hospital | | | Zuowei Hu* | Department of Oncology, Wuhan No.1 Hospital | 827823053@qq.com |
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| 中文摘要: |
| 目的：探讨LncRNA AGAP2-AS1在肺癌发生发展的机制及铁死亡的关系
方法：在目前的研究中，肺癌组织中的AGAP2-AS1水平与患者的TNM分期显著相关，并且肺癌组织的AGAP2-AS1水平显著高于健康组织。从生存曲线来看，AGAP2-AS1升高的患者预后明显低于AGAP2-AS1降低的患者。在功能上，下调AGAP2-AS1能够抑制肺癌细胞的生长。AGAP2-AS1的敲除，CCK-8实验及流式细胞仪检测，能够在肺癌细胞中诱导铁死亡。然而，FERSINT-1恢复了其中一个结果，而Erastin则诱导了肺癌细胞的死亡。敲除AGAP2-AS1，用Erastin治疗的肺癌细胞显示出GSH水平的显著下降。
结果：下调AGAP2-AS1能够抑制肺癌细胞的生长，并诱导Erastin介导的铁死亡。用Erastin治疗的肺癌细胞显示出GSH水平的显著下降。AGAP2-AS1通过IGF2BP2增强了SLC7A11 mRNA的稳定性。
结论：我们发现了AGAP2-AS1的一种新的生物学行为以及在铁死亡和促进肺癌发生发展的潜在机制，这可能有助于寻找新的肺癌治疗方法。 |
| 英文摘要: |
| Objective The initiation and progression of lung carcinomas are critically regulated by long non-coding
RNAs (lncRNAs). However, the role of lncRNAs in the pathways causing lung cancer remains unknown.
Methods Cell morphology was regularly observed using an inverted phase-contrast microscope.
Cell viability was assessed using CCK-8 according to the manufacturer’s instructions. Total RNA was
retrotranscribed from each specimen using the RNAiso Plus Kit. The RT-PCR data were calculated using
the Ct approach for comparison. Flow cytometric analyses were prepared by Click-iT? Plus TUNEL Assay
for In Situ apoptosis detection, with Alexa Fluor? 594 dye, as instructed. RNA immunoprecipitation assays
were used to determine RNA concentration.
Results Activated natural killer cells repeat and PH domain-containing protein 2 antisense RNA 1 (AGAP2-
AS1) levels in cancerous tissues were significantly correlated with cancerous tumor node metastasis (TNM)
stage, with cancerous AGAP2-AS1 levels being higher in cancerous tissues than healthy tissues. Patients
withelevated AGAP2-AS1 levels had considerably worse outcomes than those with reduced AGAP2-AS1
levels,regardless of the progression-free or overall survival. Functionally, AGAP2-AS1 downregulation
represseslung cancer cell growth. AGAP2-AS1 elimination induces erastin-mediated ferroptosis in lung
cancer cells.However, the ferritin inhibitor FERSINT-1 negated this result, whereas ERASTIN induced lung
cancer cellmortality. After AGAP2-AS1 silencing, erastin-treated lung cancer cells showed a remarkable
decrease inGSH levels. These results indicated that AGAP2-AS1 enhanced the stabilization of SLC7A11
mRNA via Recombinant Insulin Like Growth Factor Binding Protein 2(IGF BP2). Patients with elevated
AGAP2-AS1 had considerably worse outcomes. Down-regulating AGAP2-AS1 was able to repress lung
cancer cell growth and induce greater Erastin-mediated ferroptosis. Lungcancer cells treated with Erastin
exhibited a remarkable decrease inglutathione (GSH) levels. The mechanical findingsindicated that AGAP2-
AS1 enhanced the stabilization of SLC7A11 mRNA via the IGF2BP2.
Conclusion We identified a novel effect of AGAP2-AS1 on TNM staging and the prognosis of patientswith
lungcancer by modulating SLC7A11 mRNA stability and ferroptosis. |
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