PMID- 36209111
OWN - NLM
STAT- MEDLINE
DCOM- 20221011
LR  - 20221024
IS  - 1756-8722 (Electronic)
IS  - 1756-8722 (Linking)
VI  - 15
IP  - 1
DP  - 2022 Oct 8
TI  - Cancer-associated fibroblast-specific lncRNA LINC01614 enhances glutamine uptake 
      in lung adenocarcinoma.
PG  - 141
LID - 10.1186/s13045-022-01359-4 [doi]
LID - 141
AB  - BACKGROUND: Besides featured glucose consumption, recent studies reveal that 
      cancer cells might prefer "addicting" specific energy substrates from the tumor 
      microenvironment (TME); however, the underlying mechanisms remain unclear. 
      METHODS: Fibroblast-specific long noncoding RNAs were screened using RNA-seq data 
      of our NJLCC cohort, TCGA, and CCLE datasets. The expression and package of 
      LINC01614 into exosomes were identified using flow cytometric sorting, 
      fluorescence in situ hybridization (FISH), and quantitative reverse transcription 
      polymerase chain reaction (RT-PCR). The transfer and functional role of LINC01614 
      in lung adenocarcinoma (LUAD) and CAFs were investigated using 
      4-thiouracil-labeled RNA transfer and gain- and loss-of-function approaches. RNA 
      pull-down, RNA immunoprecipitation, dual-luciferase assay, gene expression 
      microarray, and bioinformatics analysis were performed to investigate the 
      underlying mechanisms involved. RESULTS: We demonstrate that cancer-associated 
      fibroblasts (CAFs) in LUAD primarily enhance the glutamine metabolism of cancer 
      cells. A CAF-specific long noncoding RNA, LINC01614, packaged by CAF-derived 
      exosomes, mediates the enhancement of glutamine uptake in LUAD cells. 
      Mechanistically, LINC01614 directly interacts with ANXA2 and p65 to facilitate 
      the activation of NF-kappaB, which leads to the upregulation of the glutamine 
      transporters SLC38A2 and SLC7A5 and eventually enhances the glutamine influx of 
      cancer cells. Reciprocally, tumor-derived proinflammatory cytokines upregulate 
      LINC01614 in CAFs, constituting a feedforward loop between CAFs and cancer cells. 
      Blocking exosome-transmitted LINC01614 inhibits glutamine addiction and LUAD 
      growth in vivo. Clinically, LINC01614 expression in CAFs is associated with the 
      glutamine influx and poor prognosis of patients with LUAD. CONCLUSION: Our study 
      highlights the therapeutic potential of targeting a CAF-specific lncRNA to 
      inhibit glutamine utilization and cancer progression in LUAD.
CI  - (c) 2022. The Author(s).
FAU - Liu, Tongyan
AU  - Liu T
AD  - Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and 
      Translational Cancer Research, Jiangsu Cancer Hospital and Nanjing Medical 
      University Affiliated Cancer Hospital and Jiangsu Institute of Cancer Research, 
      Nanjing, 21009, People's Republic of China.
AD  - Department of Science and Technology, Jiangsu Cancer Hospital and Nanjing Medical 
      University Affiliated Cancer Hospital and Jiangsu Institute of Cancer Research, 
      Nanjing, 21009, People's Republic of China.
FAU - Han, Chencheng
AU  - Han C
AD  - Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and 
      Translational Cancer Research, Jiangsu Cancer Hospital and Nanjing Medical 
      University Affiliated Cancer Hospital and Jiangsu Institute of Cancer Research, 
      Nanjing, 21009, People's Republic of China.
FAU - Fang, Panqi
AU  - Fang P
AD  - Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and 
      Translational Cancer Research, Jiangsu Cancer Hospital and Nanjing Medical 
      University Affiliated Cancer Hospital and Jiangsu Institute of Cancer Research, 
      Nanjing, 21009, People's Republic of China.
FAU - Ma, Zhifei
AU  - Ma Z
AD  - Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and 
      Translational Cancer Research, Jiangsu Cancer Hospital and Nanjing Medical 
      University Affiliated Cancer Hospital and Jiangsu Institute of Cancer Research, 
      Nanjing, 21009, People's Republic of China.
FAU - Wang, Xiaoxiao
AU  - Wang X
AD  - Department of GCP Research Center, Jiangsu Province Hospital of Chinese Medicine, 
      The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 
      210029, People's Republic of China.
FAU - Chen, Hao
AU  - Chen H
AD  - Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and 
      Translational Cancer Research, Jiangsu Cancer Hospital and Nanjing Medical 
      University Affiliated Cancer Hospital and Jiangsu Institute of Cancer Research, 
      Nanjing, 21009, People's Republic of China.
FAU - Wang, Siwei
AU  - Wang S
AD  - Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and 
      Translational Cancer Research, Jiangsu Cancer Hospital and Nanjing Medical 
      University Affiliated Cancer Hospital and Jiangsu Institute of Cancer Research, 
      Nanjing, 21009, People's Republic of China.
FAU - Meng, Fanchen
AU  - Meng F
AD  - Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and 
      Translational Cancer Research, Jiangsu Cancer Hospital and Nanjing Medical 
      University Affiliated Cancer Hospital and Jiangsu Institute of Cancer Research, 
      Nanjing, 21009, People's Republic of China.
FAU - Wang, Cheng
AU  - Wang C
AD  - Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical 
      University, Nanjing, 211116, People's Republic of China.
AD  - Department of Epidemiology and Biostatistics, International Joint Research Center 
      On Environment and Human Health, Center for Global Health, School of Public 
      Health, Nanjing Medical University, Nanjing, 211116, People's Republic of China.
AD  - Department of Bioinformatics, Nanjing Medical University, Nanjing, 211166, 
      People's Republic of China.
FAU - Zhang, Erbao
AU  - Zhang E
AD  - Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical 
      University, Nanjing, 211116, People's Republic of China.
AD  - Department of Epidemiology and Biostatistics, International Joint Research Center 
      On Environment and Human Health, Center for Global Health, School of Public 
      Health, Nanjing Medical University, Nanjing, 211116, People's Republic of China.
FAU - Dong, Guozhang
AU  - Dong G
AD  - Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and 
      Translational Cancer Research, Jiangsu Cancer Hospital and Nanjing Medical 
      University Affiliated Cancer Hospital and Jiangsu Institute of Cancer Research, 
      Nanjing, 21009, People's Republic of China.
FAU - Zhu, Hongyu
AU  - Zhu H
AD  - Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and 
      Translational Cancer Research, Jiangsu Cancer Hospital and Nanjing Medical 
      University Affiliated Cancer Hospital and Jiangsu Institute of Cancer Research, 
      Nanjing, 21009, People's Republic of China.
FAU - Yin, Wenda
AU  - Yin W
AD  - Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and 
      Translational Cancer Research, Jiangsu Cancer Hospital and Nanjing Medical 
      University Affiliated Cancer Hospital and Jiangsu Institute of Cancer Research, 
      Nanjing, 21009, People's Republic of China.
FAU - Wang, Jie
AU  - Wang J
AD  - Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and 
      Translational Cancer Research, Jiangsu Cancer Hospital and Nanjing Medical 
      University Affiliated Cancer Hospital and Jiangsu Institute of Cancer Research, 
      Nanjing, 21009, People's Republic of China.
AD  - Department of Science and Technology, Jiangsu Cancer Hospital and Nanjing Medical 
      University Affiliated Cancer Hospital and Jiangsu Institute of Cancer Research, 
      Nanjing, 21009, People's Republic of China.
AD  - Biobank of Lung Cancer, Jiangsu Biobank of Clinical Resources, Nanjing, 21009, 
      People's Republic of China.
FAU - Zuo, Xianglin
AU  - Zuo X
AD  - Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and 
      Translational Cancer Research, Jiangsu Cancer Hospital and Nanjing Medical 
      University Affiliated Cancer Hospital and Jiangsu Institute of Cancer Research, 
      Nanjing, 21009, People's Republic of China.
AD  - Department of Science and Technology, Jiangsu Cancer Hospital and Nanjing Medical 
      University Affiliated Cancer Hospital and Jiangsu Institute of Cancer Research, 
      Nanjing, 21009, People's Republic of China.
AD  - Biobank of Lung Cancer, Jiangsu Biobank of Clinical Resources, Nanjing, 21009, 
      People's Republic of China.
FAU - Qiu, Mantang
AU  - Qiu M
AD  - Department of Thoracic Surgery, Peking University People's Hospital, Beijing, 
      100044, People's Republic of China.
FAU - Wang, Jinke
AU  - Wang J
AD  - State Key Laboratory of Bioelectronics, Southeast University, Nanjing, 210018, 
      People's Republic of China.
FAU - Qian, Xu
AU  - Qian X
AD  - Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical 
      University, Nanjing, 211116, People's Republic of China.
AD  - Department of Epidemiology and Biostatistics, International Joint Research Center 
      On Environment and Human Health, Center for Global Health, School of Public 
      Health, Nanjing Medical University, Nanjing, 211116, People's Republic of China.
FAU - Shen, Hongbing
AU  - Shen H
AD  - Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical 
      University, Nanjing, 211116, People's Republic of China.
AD  - Department of Epidemiology and Biostatistics, International Joint Research Center 
      On Environment and Human Health, Center for Global Health, School of Public 
      Health, Nanjing Medical University, Nanjing, 211116, People's Republic of China.
FAU - Xu, Lin
AU  - Xu L
AD  - Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and 
      Translational Cancer Research, Jiangsu Cancer Hospital and Nanjing Medical 
      University Affiliated Cancer Hospital and Jiangsu Institute of Cancer Research, 
      Nanjing, 21009, People's Republic of China.
FAU - Hu, Zhibin
AU  - Hu Z
AD  - Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical 
      University, Nanjing, 211116, People's Republic of China. zhibin_hu@njmu.edu.cn.
AD  - Department of Epidemiology and Biostatistics, International Joint Research Center 
      On Environment and Human Health, Center for Global Health, School of Public 
      Health, Nanjing Medical University, Nanjing, 211116, People's Republic of China. 
      zhibin_hu@njmu.edu.cn.
FAU - Yin, Rong
AU  - Yin R
AD  - Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and 
      Translational Cancer Research, Jiangsu Cancer Hospital and Nanjing Medical 
      University Affiliated Cancer Hospital and Jiangsu Institute of Cancer Research, 
      Nanjing, 21009, People's Republic of China. rong_yin@njmu.edu.cn.
AD  - Department of Science and Technology, Jiangsu Cancer Hospital and Nanjing Medical 
      University Affiliated Cancer Hospital and Jiangsu Institute of Cancer Research, 
      Nanjing, 21009, People's Republic of China. rong_yin@njmu.edu.cn.
AD  - Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical 
      University, Nanjing, 211116, People's Republic of China. rong_yin@njmu.edu.cn.
AD  - Biobank of Lung Cancer, Jiangsu Biobank of Clinical Resources, Nanjing, 21009, 
      People's Republic of China. rong_yin@njmu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221008
PL  - England
TA  - J Hematol Oncol
JT  - Journal of hematology & oncology
JID - 101468937
RN  - 0 (Cytokines)
RN  - 0 (Large Neutral Amino Acid-Transporter 1)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Long Noncoding)
RN  - 0RH81L854J (Glutamine)
RN  - EC 1.13.12.- (Luciferases)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - *Adenocarcinoma/genetics
MH  - *Cancer-Associated Fibroblasts/pathology
MH  - Cytokines/metabolism
MH  - Gene Expression Regulation, Neoplastic
MH  - Glucose/metabolism
MH  - Glutamine/metabolism
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Large Neutral Amino Acid-Transporter 1/genetics/metabolism
MH  - Luciferases/genetics/metabolism
MH  - Lung/pathology
MH  - *Lung Neoplasms/pathology
MH  - NF-kappa B/metabolism
MH  - *RNA, Long Noncoding/genetics/metabolism
MH  - Tumor Microenvironment
PMC - PMC9548164
OTO - NOTNLM
OT  - Cancer-associated fibroblasts
OT  - Glutamine
OT  - Long noncoding RNA
OT  - Metabolic reprograming
OT  - Tumor microenvironment
COIS- The authors declare no competing interests.
EDAT- 2022/10/09 06:00
MHDA- 2022/10/12 06:00
PMCR- 2022/10/08
CRDT- 2022/10/08 23:18
PHST- 2022/06/28 00:00 [received]
PHST- 2022/10/02 00:00 [accepted]
PHST- 2022/10/08 23:18 [entrez]
PHST- 2022/10/09 06:00 [pubmed]
PHST- 2022/10/12 06:00 [medline]
PHST- 2022/10/08 00:00 [pmc-release]
AID - 10.1186/s13045-022-01359-4 [pii]
AID - 1359 [pii]
AID - 10.1186/s13045-022-01359-4 [doi]
PST - epublish
SO  - J Hematol Oncol. 2022 Oct 8;15(1):141. doi: 10.1186/s13045-022-01359-4.