PMID- 35857905
OWN - NLM
STAT- MEDLINE
DCOM- 20220722
LR  - 20221005
IS  - 2001-1326 (Electronic)
IS  - 2001-1326 (Linking)
VI  - 12
IP  - 7
DP  - 2022 Jul
TI  - Cancer-associated fibroblast-derived exosomal microRNA-20a suppresses the 
      PTEN/PI3K-AKT pathway to promote the progression and chemoresistance of non-small 
      cell lung cancer.
PG  - e989
LID - 10.1002/ctm2.989 [doi]
LID - e989
AB  - BACKGROUND: Cancer-associated fibroblasts (CAFs) contributes to overall tumor 
      progression. In the current survey, we explored the ability of microRNA-20a 
      (miR-20a) within these CAF-derived exosomes to influence non-small-cell lung 
      cancer (NSCLC) progression. MATERIALS AND METHODS: Normal tissue-associated 
      fibroblasts (NAFs) and CAFs were collected from samples of NSCLC patient tumors 
      and paracancerous lung tissues. Exosomes derived from these cells were then 
      characterized via Western blotting, nanoparticle tracking analyses, and 
      transmission electron microscopy. The expression of miR-20a was assessed via qPCR 
      and fluorescence in situ hybridization (FISH). CCK-8, EdU uptake, and colony 
      formation assessments were used for evaluating tumor proliferation, while Hoechst 
      staining was performed to monitor the in vitro apoptotic death of tumor cells. A 
      model of xenograft tumor established in nude mice was also used to evaluate in 
      vivo tumor responses. RESULTS: CAF-derived exosomes exhibited miR-20a 
      upregulation and promoted NSCLC cell proliferation and resistance to cisplatin 
      (DDP). Mechanistically, CAF-derived exosomes were discovered to transmit miR-20a 
      to tumor cells wherein it was able to target PTEN to enhance DDP resistance and 
      proliferation. Associated PTEN downregulation following exosome-derived miR-20a 
      treatment enhanced PI3K/AKT pathway activation. CONCLUSION: The achieved outcomes 
      explain that CAFs can release miR-20a-containing exosomes capable of promoting 
      NSCLC progression and chemoresistance, highlighting this pathway as a possible 
      therapeutic target in NSCLC.
CI  - (c) 2022 The Authors. Clinical and Translational Medicine published by John Wiley & 
      Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.
FAU - Shi, Lin
AU  - Shi L
AD  - Department of Traditional Chinese Medicine, Zhujiang Hospital of Southern Medical 
      University, Guangzhou, China.
FAU - Zhu, Weiliang
AU  - Zhu W
AD  - Department of Cancer Center, Zhujiang Hospital of Southern Medical University, 
      Guangzhou, China.
FAU - Huang, Yuanyuan
AU  - Huang Y
AD  - Department of VIP Region, State Key Laboratory of Oncology in South China, 
      Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer 
      Center, Guangzhou, China.
FAU - Zhuo, Lin
AU  - Zhuo L
AD  - Department of Traditional Chinese Medicine, Zhujiang Hospital of Southern Medical 
      University, Guangzhou, China.
FAU - Wang, Siyun
AU  - Wang S
AD  - Department of Traditional Chinese Medicine, Zhujiang Hospital of Southern Medical 
      University, Guangzhou, China.
FAU - Chen, Shaobing
AU  - Chen S
AD  - Department of Traditional Chinese Medicine, Zhujiang Hospital of Southern Medical 
      University, Guangzhou, China.
FAU - Zhang, Bei
AU  - Zhang B
AD  - Department of VIP Region, State Key Laboratory of Oncology in South China, 
      Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer 
      Center, Guangzhou, China.
FAU - Ke, Bin
AU  - Ke B
AUID- ORCID: 0000-0001-6242-9898
AD  - Department of VIP Region, State Key Laboratory of Oncology in South China, 
      Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer 
      Center, Guangzhou, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Transl Med
JT  - Clinical and translational medicine
JID - 101597971
RN  - 0 (MIRN20a microRNA, human)
RN  - 0 (MicroRNAs)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
RN  - EC 3.1.3.67 (PTEN protein, human)
SB  - IM
MH  - Animals
MH  - *Cancer-Associated Fibroblasts/metabolism/pathology
MH  - *Carcinoma, Non-Small-Cell Lung/drug therapy/genetics/metabolism
MH  - Drug Resistance, Neoplasm/genetics
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - *Lung Neoplasms/drug therapy/genetics/metabolism
MH  - Mice
MH  - Mice, Nude
MH  - *MicroRNAs/genetics/metabolism
MH  - PTEN Phosphohydrolase/genetics/metabolism
MH  - Phosphatidylinositol 3-Kinases/genetics/metabolism
MH  - Proto-Oncogene Proteins c-akt/genetics/metabolism
PMC - PMC9299573
OTO - NOTNLM
OT  - CAF
OT  - NSCLC
OT  - PTEN
OT  - exosome
OT  - microRNA-20a
COIS- The authors have no relevant financial or non-financial interests to disclose.
EDAT- 2022/07/21 06:00
MHDA- 2022/07/23 06:00
PMCR- 2022/07/20
CRDT- 2022/07/20 15:03
PHST- 2022/07/02 00:00 [revised]
PHST- 2022/03/08 00:00 [received]
PHST- 2022/07/07 00:00 [accepted]
PHST- 2022/07/20 15:03 [entrez]
PHST- 2022/07/21 06:00 [pubmed]
PHST- 2022/07/23 06:00 [medline]
PHST- 2022/07/20 00:00 [pmc-release]
AID - CTM2989 [pii]
AID - 10.1002/ctm2.989 [doi]
PST - ppublish
SO  - Clin Transl Med. 2022 Jul;12(7):e989. doi: 10.1002/ctm2.989.