PMID- 32929075
OWN - NLM
STAT- MEDLINE
DCOM- 20210420
LR  - 20210914
IS  - 2041-4889 (Electronic)
VI  - 11
IP  - 9
DP  - 2020 Sep 14
TI  - MT1DP loaded by folate-modified liposomes sensitizes erastin-induced ferroptosis 
      via regulating miR-365a-3p/NRF2 axis in non-small cell lung cancer cells.
PG  - 751
LID - 10.1038/s41419-020-02939-3 [doi]
LID - 751
AB  - Although ferroptosis has been recognized as a novel antitumoral treatment, high 
      expression of nuclear factor erythroid 2-related factor 2 (NRF2) has been 
      reported to be an antioxidant transcript factor that protects malignant cells 
      from ferroptosis. Previous findings indicated that metallothionein 1D pseudogene 
      (MT1DP), a long noncoding RNA (lncRNA), functioned to aggravate oxidative stress 
      by repressing antioxidation. Here we aimed at assessing whether MT1DP could 
      regulate erastin-induced ferroptosis on non-small cell lung cancer (NSCLC) and 
      elucidating the mechanism. We found that ectopic expression of MT1DP sensitized 
      A549 and H1299 cells to erastin-induced ferroptosis through downregulation of 
      NRF2; in addition, ectopic MT1DP upregulated malondialdehyde (MDA) and reactive 
      oxygen species (ROS) levels, increased intracellular ferrous iron concentration, 
      and reduced glutathione (GSH) levels in cancer cells exposed to erastin, whereas 
      downregulation of MT1DP showed the opposite effect. RNA pulldown assay and 
      dual-luciferase reporter assay confirmed that MT1DP modulated the expression of 
      NRF2 via stabilizing miR-365a-3p. As low solubility of erastin limits its 
      efficient application, we further prepared folate (FA)-modified liposome (FA-LP) 
      nanoparticles for targeted co-delivery of erastin and MT1DP to enhance the 
      bioavailability and the efficiency of the drug/gene combination. 
      Erastin/MT1DP@FA-LPs (E/M@FA-LPs) sensitized erastin-induced ferroptosis with 
      decreased cellular GSH levels and elevated lipid ROS. In vivo analysis showed 
      that E/M@FA-LPs had a favorable therapeutic effect on lung cancer xenografts. In 
      short, our findings identify a novel strategy to elevate erastin-induced 
      ferroptosis in NSCLCs acting through the MT1DP/miR-365a-3p/NRF2 axis.
FAU - Gai, Chengcheng
AU  - Gai C
AD  - Department of Pathology, Weifang Medical University, Weifang, Shandong Province, 
      261014, China.
FAU - Liu, Chuanliang
AU  - Liu C
AD  - The Second Department of Health Care, Weifang People's Hospital, Weifang, 
      Shandong Province, 261041, China.
FAU - Wu, Xinghan
AU  - Wu X
AD  - Department of Pathology, Weifang Medical University, Weifang, Shandong Province, 
      261014, China.
FAU - Yu, Mengyu
AU  - Yu M
AD  - Department of Pathology, Weifang Medical University, Weifang, Shandong Province, 
      261014, China.
FAU - Zheng, Jie
AU  - Zheng J
AD  - Department of Pathology, Weifang Medical University, Weifang, Shandong Province, 
      261014, China.
FAU - Zhang, Weifen
AU  - Zhang W
AD  - Department of Pharmacology, Weifang Medical University, Weifang, Shandong 
      Province, 261014, China.
FAU - Lv, Shijun
AU  - Lv S
AD  - Department of Pathology, Weifang Medical University, Weifang, Shandong Province, 
      261014, China. sjlu@wfmc.edu.cn.
FAU - Li, Wentong
AU  - Li W
AD  - Department of Pathology, Weifang Medical University, Weifang, Shandong Province, 
      261014, China. liwentong11@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200914
PL  - England
TA  - Cell Death Dis
JT  - Cell death & disease
JID - 101524092
RN  - 0 (Liposomes)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (NFE2L2 protein, human)
RN  - 0 (Piperazines)
RN  - 0 (erastin)
SB  - IM
MH  - Animals
MH  - Carcinoma, Non-Small-Cell Lung/*drug therapy
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Ferroptosis/*drug effects
MH  - Humans
MH  - Liposomes/*metabolism
MH  - Lung Neoplasms/*drug therapy
MH  - Mice
MH  - NF-E2-Related Factor 2/*drug effects
MH  - Piperazines/pharmacology/*therapeutic use
MH  - Transfection
PMC - PMC7490417
COIS- The authors declare that they have no competing interests.
EDAT- 2020/09/16 06:00
MHDA- 2021/04/21 06:00
PMCR- 2020/09/14
CRDT- 2020/09/15 05:42
PHST- 2020/02/18 00:00 [received]
PHST- 2020/08/26 00:00 [accepted]
PHST- 2020/08/10 00:00 [revised]
PHST- 2020/09/15 05:42 [entrez]
PHST- 2020/09/16 06:00 [pubmed]
PHST- 2021/04/21 06:00 [medline]
PHST- 2020/09/14 00:00 [pmc-release]
AID - 10.1038/s41419-020-02939-3 [pii]
AID - 2939 [pii]
AID - 10.1038/s41419-020-02939-3 [doi]
PST - epublish
SO  - Cell Death Dis. 2020 Sep 14;11(9):751. doi: 10.1038/s41419-020-02939-3.