PMID- 36760260
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230211
IS  - 2305-5839 (Print)
IS  - 2305-5847 (Electronic)
IS  - 2305-5839 (Linking)
VI  - 11
IP  - 1
DP  - 2023 Jan 15
TI  - Inhibition of the AKT1/mTOR pathway through SIRT6 over expression downregulated 
      the expression of programmed death-ligand 1 and prolonged overall survival in 
      lung adenocarcinoma.
PG  - 21
LID - 10.21037/atm-22-6218 [doi]
LID - 21
AB  - BACKGROUND: Programmed death-ligand 1 (PD-L1) is a common biomarker of immune 
      checkpoint inhibitors (ICIs). The purpose of our study was to investigate the 
      relationship between Sirtuin 6 (SIRT6) and PD-L1 expressions in lung 
      adenocarcinoma. METHODS: Recombinant plasmids containing green fluorescent 
      protein (GFP)/no SIRT6 (h-NULL) and GFP/SIRT6 (h-SIRT6) were constructed and 
      transfected into A549 cells by lentivirus as vector. The experiment was divided 
      into control, h-NULL and h-SIRT6 groups. We detected apoptosis and the cell cycle 
      by flow cytometry and observed migration and proliferation by wound-healing 
      assays and methyl thiazolyl tetrazolium. The expressions of SIRT6, PD-L1, 
      serine/threonine protein kinase-1 (AKT1), mammalian target of rapamycin (mTOR), 
      B-cell lymphoma-2 (BCL-2) associated X protein (BAX), and BCL-2 were detected by 
      real-time fluorescence quantitative reverse transcription polymerase chain 
      reaction (qRT-PCR) and Western blot. We retrospectively analyzed the relationship 
      between SIRT6 expression and survival in lung adenocarcinoma treated by ICIs. 
      RESULTS: The expression of BAX, apoptosis rate, and proportion of G0G1 and G2M 
      phases in the h-SIRT6 group were higher than in the control and h-NULL groups 
      (P<0.05). The expressions of PD-L1, BCL-2, AKT1, and mTOR migration and 
      proliferation rates and proportion of S phase in the h-SIRT6 group were lower 
      than in the control and h-NULL groups (P<0.05). Survival in lung adenocarcinoma 
      with high SIRT6 expression was better than with low SIRT6 expression. 
      CONCLUSIONS: SIRT6 over expression, through the inhibition of the AKT1/mTOR 
      pathway, down-regulated PD-L1 expression, influenced biological behaviors, and 
      prolonged survival of lung adenocarcinoma. SIRT6 expression may be a potential 
      gene biomarker for immunotherapy in lung adenocarcinoma.
CI  - 2023 Annals of Translational Medicine. All rights reserved.
FAU - Yuan, Zi-Fu
AU  - Yuan ZF
AD  - Department of Oncology, the Affiliated Hospital of Southwest Medical University, 
      Luzhou, China.
FAU - Lin, Yi-Dong
AU  - Lin YD
AD  - Department of Oncology, the Affiliated Hospital of Southwest Medical University, 
      Luzhou, China.
FAU - Wu, Gui-Shu
AU  - Wu GS
AD  - Department of Oncology, the Affiliated Hospital of Southwest Medical University, 
      Luzhou, China.
FAU - Li, Lin
AU  - Li L
AD  - Department of Oncology, First People's Hospital of Neijiang, Neijiang, China.
FAU - Yang, Jing-Pin
AU  - Yang JP
AD  - Department of Oncology, the First Hospital of Guangyuan, Guangyuan, China.
FAU - Zhang, Jian-Wen
AU  - Zhang JW
AD  - Department of Oncology, the Affiliated Hospital of Southwest Medical University, 
      Luzhou, China.
AD  - Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, 
      Luzhou, China.
AD  - Academician (Expert) workstation of Sichuan Province, Luzhou, China.
LA  - eng
PT  - Journal Article
PL  - China
TA  - Ann Transl Med
JT  - Annals of translational medicine
JID - 101617978
PMC - PMC9906195
OTO - NOTNLM
OT  - A549 cell line
OT  - Sirtuin 6 (SIRT6)
OT  - lentiviral
OT  - lung adenocarcinoma
OT  - programmed death-ligand 1 (PD-L1)
COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure 
      form (available at 
      https://atm.amegroups.com/article/view/10.21037/atm-22-6218/coif). The authors 
      have no conflicts of interest to declare.
EDAT- 2023/02/11 06:00
MHDA- 2023/02/11 06:01
PMCR- 2023/01/15
CRDT- 2023/02/10 02:54
PHST- 2022/11/21 00:00 [received]
PHST- 2023/01/05 00:00 [accepted]
PHST- 2023/02/10 02:54 [entrez]
PHST- 2023/02/11 06:00 [pubmed]
PHST- 2023/02/11 06:01 [medline]
PHST- 2023/01/15 00:00 [pmc-release]
AID - atm-11-01-21 [pii]
AID - 10.21037/atm-22-6218 [doi]
PST - ppublish
SO  - Ann Transl Med. 2023 Jan 15;11(1):21. doi: 10.21037/atm-22-6218.