PMID- 34971743
OWN - NLM
STAT- MEDLINE
DCOM- 20220118
LR  - 20220118
IS  - 1873-6424 (Electronic)
IS  - 0269-7491 (Linking)
VI  - 296
DP  - 2022 Mar 1
TI  - LincRNA-p21 promotes p21-mediated cell cycle arrest in benzene-induced 
      hematotoxicity by sponging miRNA-17-5p.
PG  - 118706
LID - S0269-7491(21)02288-0 [pii]
LID - 10.1016/j.envpol.2021.118706 [doi]
AB  - Benzene is widely employed in manufacturing and causes hematotoxic effects and 
      leukemia in humans. A long intergenic noncoding RNA (lincRNA)-microRNA 
      (miRNA)-mRNA coexpression and competing endogenous RNA (ceRNA) regulatory network 
      was constructed by bioinformatics analysis based on a benzene-induced aplastic 
      anemia (BIAA) mouse model. In this population-based study, we observed a trend 
      consistent with that in the BIAA mice: lincRNA-p21 and p21 were upregulated, 
      while miRNA-17-5p expression was downregulated in benzene-exposed workers. 
      Moreover, multiple linear regressions indicated that lincRNA-p21 was negatively 
      associated with white blood cell (WBC) counts. Predictive thresholds of 
      hematotoxicity were identified by ROC curve analysis with S-phenylmercapturic 
      acid (SPMA) and lincRNA-p21 showing a better predictive ability than the other 
      parameters and the combination of SPMA and lincRNA-p21 exhibiting the highest 
      predictive value for hematotoxicity. LincRNA-p21 was predominantly present in the 
      cytoplasm of bone marrow cells (BMCs) and K562 cells as assessed by fluorescence 
      in situ hybridization (FISH). Upon exploring the underlying mechanism by which 
      lincRNA-p21 mediates benzene-induced hematotoxicity, we observed that the 
      negative regulation of 1,4-benzoquinone (1,4-BQ) on cell cycle arrest and 
      inhibition of K562 cell proliferation was partially relieved by lincRNA-p21 
      knockdown, which can inhibit the expression of P21 and thereby suppress the toxic 
      effects of 1,4-BQ. Finally, dual-luciferase reporter gene and RIP assay showed 
      that, by acting as a sponge, lincRNA-p21 reduced the activity of miRNA-17-5p and 
      consequently increased the expression of p21. In conclusion, our research 
      suggested that benzene induces hematotoxicity via the lincRNA-p21/miRNA-17-5p/p21 
      signaling which might contribute to the underlying mechanism of lincRNA-p21 in 
      benzene-induced hematotoxicity. Therefore, lincRNA-p21 can serve as a potential 
      biomarker for the early detection of hematopoiesis inhibition in individuals with 
      long-term exposure to low-dose benzene.
CI  - Copyright (c) 2021 Elsevier Ltd. All rights reserved.
FAU - Wang, Boshen
AU  - Wang B
AD  - Key Laboratory of Environmental Medicine Engineering of Ministry of Education, 
      School of Public Health, Southeast University, Nanjing 210009, Jiangsu, China; 
      Jiangsu Provincial Center for Disease Prevention and Control, Nanjing 210000, 
      Jiangsu, China.
FAU - Xu, Shouxiang
AU  - Xu S
AD  - Key Laboratory of Environmental Medicine Engineering of Ministry of Education, 
      School of Public Health, Southeast University, Nanjing 210009, Jiangsu, China.
FAU - Wang, Tong
AU  - Wang T
AD  - Key Laboratory of Environmental Medicine Engineering of Ministry of Education, 
      School of Public Health, Southeast University, Nanjing 210009, Jiangsu, China.
FAU - Xu, Kai
AU  - Xu K
AD  - Key Laboratory of Environmental Medicine Engineering of Ministry of Education, 
      School of Public Health, Southeast University, Nanjing 210009, Jiangsu, China.
FAU - Yin, Lihong
AU  - Yin L
AD  - Key Laboratory of Environmental Medicine Engineering of Ministry of Education, 
      School of Public Health, Southeast University, Nanjing 210009, Jiangsu, China.
FAU - Li, Xiaoqin
AU  - Li X
AD  - Yangzhou Center for Disease Control and Prevention, China.
FAU - Sun, Rongli
AU  - Sun R
AD  - Key Laboratory of Environmental Medicine Engineering of Ministry of Education, 
      School of Public Health, Southeast University, Nanjing 210009, Jiangsu, China.
FAU - Pu, Yuepu
AU  - Pu Y
AD  - Key Laboratory of Environmental Medicine Engineering of Ministry of Education, 
      School of Public Health, Southeast University, Nanjing 210009, Jiangsu, China.
FAU - Zhang, Juan
AU  - Zhang J
AD  - Key Laboratory of Environmental Medicine Engineering of Ministry of Education, 
      School of Public Health, Southeast University, Nanjing 210009, Jiangsu, China. 
      Electronic address: 101011288@seu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20211228
PL  - England
TA  - Environ Pollut
JT  - Environmental pollution (Barking, Essex : 1987)
JID - 8804476
RN  - 0 (MicroRNAs)
RN  - 0 (RNA, Long Noncoding)
RN  - J64922108F (Benzene)
SB  - IM
MH  - Animals
MH  - Benzene/toxicity
MH  - Cell Cycle Checkpoints
MH  - In Situ Hybridization, Fluorescence
MH  - Mice
MH  - *MicroRNAs/genetics
MH  - *RNA, Long Noncoding/genetics
OTO - NOTNLM
OT  - Benzene
OT  - Hematotoxicity
OT  - ceRNA
OT  - lincRNA-p21
EDAT- 2022/01/01 06:00
MHDA- 2022/01/19 06:00
CRDT- 2021/12/31 20:10
PHST- 2021/07/14 00:00 [received]
PHST- 2021/12/15 00:00 [revised]
PHST- 2021/12/15 00:00 [accepted]
PHST- 2022/01/01 06:00 [pubmed]
PHST- 2022/01/19 06:00 [medline]
PHST- 2021/12/31 20:10 [entrez]
AID - S0269-7491(21)02288-0 [pii]
AID - 10.1016/j.envpol.2021.118706 [doi]
PST - ppublish
SO  - Environ Pollut. 2022 Mar 1;296:118706. doi: 10.1016/j.envpol.2021.118706. Epub 
      2021 Dec 28.