PMID- 30962263
OWN - NLM
STAT- MEDLINE
DCOM- 20200617
LR  - 20231213
IS  - 1573-4935 (Electronic)
IS  - 0144-8463 (Print)
IS  - 0144-8463 (Linking)
VI  - 39
IP  - 4
DP  - 2019 Apr 30
TI  - miR-140-5p induces cell apoptosis and decreases Warburg effect in chronic myeloid 
      leukemia by targeting SIX1.
LID - BSR20190150 [pii]
LID - 10.1042/BSR20190150 [doi]
AB  - microRNAs (miRNA), as tumor suppressors or oncogenes, are involved in modulating 
      cancer cell behavior, including cell proliferation and apoptosis. The miR-140-5p 
      acts as a tumor suppressor in several tumors, but the role of miR-140-5p in 
      chronic myeloid leukemia (CML) remains unclear. Here, we investigated the 
      suppression of miR-140-5p in CML patients and CML cell lines using quantitative 
      PCR (qPCR) and fluorescence in situ hybridization (FISH). Overexpression 
      miR-140-5p in CML cells significantly inhibited cell proliferation as revealed by 
      the CCK-8 assay and promoted cell apoptosis as revealed by flow cytometry. 
      Moreover, the sine oculis homeobox 1 (SIX1) gene had been confirmed as a direct 
      target of miR-140-5p using bioinformatics analysis and luciferase reporter 
      assays. Overexpression of miR-140-5p decreased the SIX1 protein level in CML 
      cells. SIX1 mRNA and protein levels were significantly up-regulated in CML 
      patients and CML cell lines. Knockdown of SIX1 expression significantly inhibited 
      CML cell proliferation and promoted cell apoptosis. Furthermore, SIX1 as a 
      transcriptional factor positively regulated pyruvate kinase isozyme type M2 
      (PKM2) expression and played an important role in the Warburg effect. In 
      addition, these findings indicated that miR-140-5p functions as a tumor 
      suppressor and plays a critical role in CML cell apoptosis and metabolism by 
      targeting SIX1. Moreover, the miR-140-5p/SIX1 axis may be a potential therapeutic 
      target in CML.
CI  - (c) 2019 The Author(s).
FAU - Nie, Zi-Yuan
AU  - Nie ZY
AD  - Department of Hematology, The Second Hospital of Hebei Medical University, 215 
      Heping W Rd, Shijiazhuang 050000, China.
FAU - Liu, Xiao-Jun
AU  - Liu XJ
AD  - Department of Hematology, The Second Hospital of Hebei Medical University, 215 
      Heping W Rd, Shijiazhuang 050000, China.
FAU - Zhan, Ying
AU  - Zhan Y
AD  - Department of Hematology, The Second Hospital of Hebei Medical University, 215 
      Heping W Rd, Shijiazhuang 050000, China.
FAU - Liu, Meng-Han
AU  - Liu MH
AD  - Department of Hematology, The Second Hospital of Hebei Medical University, 215 
      Heping W Rd, Shijiazhuang 050000, China.
FAU - Zhang, Xiao-Yan
AU  - Zhang XY
AD  - Department of Hematology, The Second Hospital of Hebei Medical University, 215 
      Heping W Rd, Shijiazhuang 050000, China.
FAU - Li, Zi-Ye
AU  - Li ZY
AD  - Department of Hematology, The Second Hospital of Hebei Medical University, 215 
      Heping W Rd, Shijiazhuang 050000, China.
FAU - Lu, Ya-Qiong
AU  - Lu YQ
AD  - Department of Hematology, The Second Hospital of Hebei Medical University, 215 
      Heping W Rd, Shijiazhuang 050000, China.
FAU - Luo, Jian-Min
AU  - Luo JM
AUID- ORCID: 0000-0002-8811-7187
AD  - Department of Hematology, The Second Hospital of Hebei Medical University, 215 
      Heping W Rd, Shijiazhuang 050000, China luojianmin1960@126.com.
FAU - Yang, Lin
AU  - Yang L
AD  - Department of Hematology, The Second Hospital of Hebei Medical University, 215 
      Heping W Rd, Shijiazhuang 050000, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190430
PL  - England
TA  - Biosci Rep
JT  - Bioscience reports
JID - 8102797
RN  - 0 (Carrier Proteins)
RN  - 0 (Homeodomain Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (MicroRNAs)
RN  - 0 (Mirn140 microRNA, human)
RN  - 0 (SIX1 protein, human)
RN  - 0 (Thyroid Hormones)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Apoptosis/genetics
MH  - Carrier Proteins/genetics/metabolism
MH  - Cell Line, Tumor
MH  - Female
MH  - Gene Expression Regulation, Leukemic
MH  - Homeodomain Proteins/*genetics
MH  - Humans
MH  - K562 Cells
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*genetics/*pathology
MH  - Leukocytes, Mononuclear/pathology/physiology
MH  - Male
MH  - Membrane Proteins/genetics/metabolism
MH  - MicroRNAs/*genetics/metabolism
MH  - Middle Aged
MH  - Thyroid Hormones/genetics/metabolism
MH  - Thyroid Hormone-Binding Proteins
PMC - PMC6488949
OTO - NOTNLM
OT  - Chronic myeloid leukemia
OT  - PKM2
OT  - SIX1
OT  - Warburg effect
OT  - apoptosis
OT  - miR-140-5p
COIS- The authors declare that there are no competing interests associated with the 
      manuscript.
EDAT- 2019/04/10 06:00
MHDA- 2020/06/18 06:00
PMCR- 2019/04/30
CRDT- 2019/04/10 06:00
PHST- 2019/01/24 00:00 [received]
PHST- 2019/03/29 00:00 [revised]
PHST- 2019/04/06 00:00 [accepted]
PHST- 2019/04/10 06:00 [pubmed]
PHST- 2020/06/18 06:00 [medline]
PHST- 2019/04/10 06:00 [entrez]
PHST- 2019/04/30 00:00 [pmc-release]
AID - BSR20190150 [pii]
AID - 10.1042/BSR20190150 [doi]
PST - epublish
SO  - Biosci Rep. 2019 Apr 30;39(4):BSR20190150. doi: 10.1042/BSR20190150. Print 2019 
      Apr 30.