PMID- 36040682
OWN - NLM
STAT- MEDLINE
DCOM- 20230124
LR  - 20230202
IS  - 2092-9293 (Electronic)
IS  - 1976-9571 (Linking)
VI  - 45
IP  - 2
DP  - 2023 Feb
TI  - MiR-30c facilitates natural killer cell cytotoxicity to lung cancer through 
      targeting GALNT7.
PG  - 247-260
LID - 10.1007/s13258-022-01306-0 [doi]
AB  - BACKGROUND: MicroRNAs (miRNAs) have been reported to play important roles in 
      regulating natural killer (NK) cell cytotoxicity to cancer cells. OBJECTIVE: This 
      study aimed to investigate the effects and potential mechanism of miR-30c in 
      regulating NK cell cytotoxicity to lung cancer cells. METHODS: Primary NK cells 
      were derived from the peripheral blood of lung cancer and normal participants. 
      Exosomes were isolated and validated via transmission electron microscopy and 
      nanoparticle tracking analysis. The levels of miR-30c, polypeptide 
      N-acetylgalactosaminyltransferase 7 (GALNT7) and proteins in PI3K/AKT pathway 
      were determined using quantitative real-time polymerase chain reaction or western 
      blot. Tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) levels and the 
      cytotoxicity of effector NK cells to target lung cancer cells were measured via 
      enzyme linked immunosorbent assay, cell apoptosis or xenograft experiments. The 
      relationship between miR-30c and GALNT7 was analyzed by luciferase activity, RNA 
      pull-down and RNA immunoprecipitation assays. And a xenograft mice model was 
      established to verify the effect of miR-30c in regulating NK cell cytotoxicity to 
      lung cancer cells in vivo. RESULTS: NK cell-derived exosomes carrying miR-30c, 
      and miR-30c level was significantly downregulated in primary NK cells of lung 
      cancer patients. MiR-30c overexpression promoted TNF-alpha and IFN-gamma secretion and 
      enhanced the cytotoxicity of interleukin 2 (IL-2)-treated NK cells to lung cancer 
      cells, while knockdown of miR-30c played an opposite effect in regulating the 
      cytotoxicity of NK cells to lung cancer cells. GALNT7 was a target of miR-30c and 
      was negatively regulated by miR-30c. Besides, miR-30c targeted GALNT7 to exert 
      its function in regulating NK cell cytotoxicity. Furthermore, GALNT7 prompted the 
      activation of PI3K/AKT pathway in NK cells. Additionally, miR-30c overexpression 
      enhanced NK cell cytotoxicity to lung cancer cells and inhibited tumor growth in 
      vivo. CONCLUSION: miR-30c enhanced NK cell cytotoxicity to lung cancer cells via 
      decreasing GALNT7 and inactivating the PI3K/AKT pathway, suggesting that 
      regulating miR-30c expression maybe a promising approach for enhancing NK 
      cell-based antitumor therapies.
CI  - (c) 2022. The Author(s) under exclusive licence to The Genetics Society of Korea.
FAU - Gao, Fei
AU  - Gao F
AD  - Department of Oncology, The Third Hospital of Mianyang, Sichuan Mental Health 
      Center), No. 190, East Section of Jiannan Road, Sichuan, 621000, China.
FAU - Han, Jianjun
AU  - Han J
AUID- ORCID: 0000-0003-2885-3470
AD  - Department of Oncology, The Third Hospital of Mianyang, Sichuan Mental Health 
      Center), No. 190, East Section of Jiannan Road, Sichuan, 621000, China. 
      myhjj509509@163.com.
FAU - Jia, Li
AU  - Jia L
AD  - Department of Oncology, The Third Hospital of Mianyang, Sichuan Mental Health 
      Center), No. 190, East Section of Jiannan Road, Sichuan, 621000, China.
FAU - He, Jun
AU  - He J
AD  - Department of Oncology, The Third Hospital of Mianyang, Sichuan Mental Health 
      Center), No. 190, East Section of Jiannan Road, Sichuan, 621000, China.
FAU - Wang, Yun
AU  - Wang Y
AD  - Department of Oncology, The Third Hospital of Mianyang, Sichuan Mental Health 
      Center), No. 190, East Section of Jiannan Road, Sichuan, 621000, China.
FAU - Chen, Mi
AU  - Chen M
AD  - Department of Oncology, The Third Hospital of Mianyang, Sichuan Mental Health 
      Center), No. 190, East Section of Jiannan Road, Sichuan, 621000, China.
FAU - Liu, Xiaojun
AU  - Liu X
AD  - Department of Oncology, The Third Hospital of Mianyang, Sichuan Mental Health 
      Center), No. 190, East Section of Jiannan Road, Sichuan, 621000, China.
FAU - He, Xia
AU  - He X
AD  - Department of Oncology, The Third Hospital of Mianyang, Sichuan Mental Health 
      Center), No. 190, East Section of Jiannan Road, Sichuan, 621000, China.
LA  - eng
PT  - Journal Article
DEP - 20220830
PL  - Korea (South)
TA  - Genes Genomics
JT  - Genes & genomics
JID - 101481027
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - 0 (MicroRNAs)
SB  - IM
MH  - Humans
MH  - Animals
MH  - Mice
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - *MicroRNAs/genetics/metabolism
MH  - Killer Cells, Natural/metabolism
MH  - *Lung Neoplasms/genetics/metabolism
OTO - NOTNLM
OT  - Cytotoxicity
OT  - GALNT7
OT  - Lung cancer
OT  - Natural killer cells
OT  - miR-30c
EDAT- 2022/08/31 06:00
MHDA- 2023/01/25 06:00
CRDT- 2022/08/30 11:26
PHST- 2022/02/15 00:00 [received]
PHST- 2022/06/11 00:00 [accepted]
PHST- 2022/08/31 06:00 [pubmed]
PHST- 2023/01/25 06:00 [medline]
PHST- 2022/08/30 11:26 [entrez]
AID - 10.1007/s13258-022-01306-0 [pii]
AID - 10.1007/s13258-022-01306-0 [doi]
PST - ppublish
SO  - Genes Genomics. 2023 Feb;45(2):247-260. doi: 10.1007/s13258-022-01306-0. Epub 
      2022 Aug 30.