| 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. |
| 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 |
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| KeyWord:AGAP2-AS1; ferroptosis; lung cancer; mRNA stability |
| 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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| Abstract: |
| 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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