PMID- 35288170
OWN - NLM
STAT- MEDLINE
DCOM- 20220429
LR  - 20220531
IS  - 1090-2422 (Electronic)
IS  - 0014-4827 (Linking)
VI  - 414
IP  - 2
DP  - 2022 May 15
TI  - Extracellular vesicle-mediated delivery of miR-127-3p inhibits the proliferation 
      and invasion of choriocarcinoma cells by targeting ITGA6.
PG  - 113098
LID - S0014-4827(22)00091-X [pii]
LID - 10.1016/j.yexcr.2022.113098 [doi]
AB  - BACKGROUND: Choriocarcinoma (CC) is a highly aggressive malignant tumor that 
      mostly occurs in women of childbearing age. Chemotherapy is the main treatment 
      for CC, but it has side effects and causes drug resistance, which can lead to 
      treatment failure. Extracellular vesicles (EVs) that deliver microRNAs (miRNAs) 
      have emerged as a novel and promising therapeutic tool for inhibiting tumor 
      progression and metastasis. This research aimed to study the effects of 
      miR-127-3p-enriched EVs (EV-miR-127-3p) on CC and underlying mechanisms. METHODS: 
      Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and 
      western blotting were performed to determine the miR-127-3p and integrin subunit 
      alpha-6 (ITGA6) expression levels. The interaction between miR-127-3p and ITGA6 
      was confirmed by a dual-luciferase reporter assay. Human umbilical cord 
      mesenchymal stem cells (hUCMSCs) were identified using flow cytometry and 
      multilineage differentiation. Uptake of labeled EVs was demonstrated using 
      immunofluorescence staining and flow cytometry assays. EV-miR-127-3p were 
      isolated from the culture medium of hUCMSCs and co-cultured with JEG-3 or JAR 
      cells to evaluate their effects on cell proliferation, invasion, migration, and 
      apoptosis, using the cell counting kit-8, Transwell, and flow cytometry assays. 
      Epithelial-mesenchymal transition (EMT) and the transforming growth factor 
      (TGF)-beta1/Smad pathway were investigated using qRT-PCR and western blotting. 
      RESULTS: The expression of miR-127-3p was downregulated, while that of ITGA6 was 
      upregulated in CC cell lines. ITGA6 was identified as a target gene of 
      miR-127-3p. EV-miR-127-3p could inhibit the proliferation, invasion, migration, 
      and promote the apoptosis of CC cells. We observed that EV-miR-127-3p suppressed 
      EMT of CC cells by targeting ITGA6. In addition, the knockdown of ITGA6 inhibited 
      the TGF-beta1/Smad pathway and reversed the EMT-promoting effect. CONCLUSION: These 
      results indicate that EV-miR-127-3p from hUCMSCs exhibits anti-tumor effects by 
      targeting ITGA6, which may be used as a novel therapeutic strategy for CC 
      treatment.
CI  - Copyright (c) 2022 Elsevier Inc. All rights reserved.
FAU - Ma, Hanbo
AU  - Ma H
AD  - Department of Obstetrics and Gynecology, Tongji Hospital of Tongji University, 
      Tongji University School of Medicine, Shanghai, China.
FAU - Weng, Fengyun
AU  - Weng F
AD  - Department of Obstetrics and Gynecology, Shangyu People's Hospital of Shaoxing, 
      Zhejiang, China.
FAU - Wang, Lang
AU  - Wang L
AD  - Department of Obstetrics and Gynecology, People's Hospital of Suiyang, Guizhou, 
      China.
FAU - Tong, Xiaowen
AU  - Tong X
AD  - Department of Obstetrics and Gynecology, Tongji Hospital of Tongji University, 
      Tongji University School of Medicine, Shanghai, China.
FAU - Yao, Yinan
AU  - Yao Y
AD  - Stem Cell Translational Research Center, Tongji Hospital of Tongji University, 
      Tongji University School of Medicine, Shanghai, China. Electronic address: 
      yinanyao@126.com.
FAU - Li, Huaifang
AU  - Li H
AD  - Department of Obstetrics and Gynecology, Tongji Hospital of Tongji University, 
      Tongji University School of Medicine, Shanghai, China. Electronic address: 
      huaifangli@126.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220311
PL  - United States
TA  - Exp Cell Res
JT  - Experimental cell research
JID - 0373226
RN  - 0 (ITGA6 protein, human)
RN  - 0 (Integrin alpha6)
RN  - 0 (MIRN127 microRNA, human)
RN  - 0 (MicroRNAs)
SB  - IM
MH  - Cell Line, Tumor
MH  - Cell Movement/genetics
MH  - Cell Proliferation/genetics
MH  - *Choriocarcinoma/genetics
MH  - *Extracellular Vesicles/genetics/metabolism
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Integrin alpha6/genetics
MH  - *MicroRNAs/genetics/metabolism
OTO - NOTNLM
OT  - Choriocarcinoma
OT  - Extracellular vesicles
OT  - Human umbilical cord mesenchymal stem cells
OT  - Integrin subunit alpha-6
OT  - miR-127-3p
EDAT- 2022/03/16 06:00
MHDA- 2022/04/30 06:00
CRDT- 2022/03/15 05:41
PHST- 2021/08/27 00:00 [received]
PHST- 2022/03/01 00:00 [revised]
PHST- 2022/03/08 00:00 [accepted]
PHST- 2022/03/16 06:00 [pubmed]
PHST- 2022/04/30 06:00 [medline]
PHST- 2022/03/15 05:41 [entrez]
AID - S0014-4827(22)00091-X [pii]
AID - 10.1016/j.yexcr.2022.113098 [doi]
PST - ppublish
SO  - Exp Cell Res. 2022 May 15;414(2):113098. doi: 10.1016/j.yexcr.2022.113098. Epub 
      2022 Mar 11.