PMID- 30698830
OWN - NLM
STAT- MEDLINE
DCOM- 20190614
LR  - 20190614
IS  - 1099-081X (Electronic)
IS  - 0142-2782 (Linking)
VI  - 40
IP  - 2
DP  - 2019 Feb
TI  - TGF-beta1 elevates P-gp and BCRP in hepatocellular carcinoma through HOTAIR/miR-145 
      axis.
PG  - 70-80
LID - 10.1002/bdd.2172 [doi]
AB  - Multidrug resistance (MDR) is common in patients and has been linked to 
      transforming growth factor-beta1 (TGF-beta1) and overexpression of drug efflux 
      transporters P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), 
      although the molecular mechanisms remain largely unknown. This study aimed to 
      investigate the mechanisms underlying TGF-beta1-induced MDR in hepatocellular 
      carcinoma (HCC) cells. It was found that TGF-beta1 upregulated HOX transcript 
      antisense RNA (HOTAIR) expression in HCC cells. When drosophila mothers against 
      decapentaplegic 4 (SMAD4) was silenced, HOTAIR expression was accordingly 
      reduced. Meanwhile, miR-145 expression was increased in the case HOTAIR was 
      silenced. If the enhancer of zeste homolog 2 (EZH2) was knocked down using small 
      interfering RNA (siRNA), miR-145 expression was decreased. Then, the regulatory 
      role of miR-145 in P-gp and BCRP expression was explored. The results showed that 
      the expression of P-gp and BCRP protein was suppressed by miR-145 through binding 
      to the 3'-untranslated regions (3'-UTRs) of P-gp and BCRP. In conclusion, our 
      study revealed a novel mechanism explaining TGF-beta1-induced MDR in HCC through 
      upregulating P-gp and BCRP via the SMAD4/HOTAIR/miR-145 axis.
CI  - (c) 2019 John Wiley & Sons, Ltd.
FAU - Kong, Jiehong
AU  - Kong J
AUID- ORCID: 0000-0002-7772-4395
AD  - Center for Drug Metabolism and Pharmacokinetics, College of Pharmaceutical 
      Sciences, Soochow University, Suzhou, 215123, China.
FAU - Qiu, Yajing
AU  - Qiu Y
AD  - Center for Drug Metabolism and Pharmacokinetics, College of Pharmaceutical 
      Sciences, Soochow University, Suzhou, 215123, China.
FAU - Li, Yuan
AU  - Li Y
AD  - Center for Drug Metabolism and Pharmacokinetics, College of Pharmaceutical 
      Sciences, Soochow University, Suzhou, 215123, China.
FAU - Zhang, Hongjian
AU  - Zhang H
AD  - Center for Drug Metabolism and Pharmacokinetics, College of Pharmaceutical 
      Sciences, Soochow University, Suzhou, 215123, China.
FAU - Wang, Weipeng
AU  - Wang W
AD  - Center for Drug Metabolism and Pharmacokinetics, College of Pharmaceutical 
      Sciences, Soochow University, Suzhou, 215123, China.
LA  - eng
GR  - 81773044/The National Natural Science Foundation of China/
GR  - 81270031/The National Natural Science Foundation of China/
GR  - 81272737/The National Natural Science Foundation of China/
GR  - 81372375/The National Natural Science Foundation of China/
GR  - 81473278/The National Natural Science Foundation of China/
PT  - Journal Article
DEP - 20190218
PL  - England
TA  - Biopharm Drug Dispos
JT  - Biopharmaceutics & drug disposition
JID - 7911226
RN  - 0 (ABCG2 protein, human)
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B, Member 1)
RN  - 0 (ATP Binding Cassette Transporter, Subfamily G, Member 2)
RN  - 0 (HOTAIR long untranslated RNA, human)
RN  - 0 (MIRN145 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (RNA, Long Noncoding)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 8A1O1M485B (Imatinib Mesylate)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics/*metabolism
MH  - ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics/*metabolism
MH  - Animals
MH  - Base Sequence
MH  - Biological Transport
MH  - CHO Cells
MH  - Carcinoma, Hepatocellular/metabolism
MH  - Cricetulus
MH  - Drug Resistance, Neoplasm
MH  - Female
MH  - HCT116 Cells
MH  - Hep G2 Cells
MH  - Humans
MH  - Imatinib Mesylate/pharmacokinetics/pharmacology
MH  - Liver Neoplasms/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - MicroRNAs/genetics/*metabolism
MH  - Neoplasm Proteins/genetics/*metabolism
MH  - RNA, Long Noncoding/genetics/*metabolism
MH  - Transforming Growth Factor beta1/*pharmacology
OTO - NOTNLM
OT  - BCRP
OT  - P-gp
OT  - TGF-beta1
OT  - hepatocellular carcinoma
OT  - miR-145
EDAT- 2019/01/31 06:00
MHDA- 2019/06/15 06:00
CRDT- 2019/01/31 06:00
PHST- 2018/10/25 00:00 [received]
PHST- 2019/01/13 00:00 [revised]
PHST- 2019/01/23 00:00 [accepted]
PHST- 2019/01/31 06:00 [pubmed]
PHST- 2019/06/15 06:00 [medline]
PHST- 2019/01/31 06:00 [entrez]
AID - 10.1002/bdd.2172 [doi]
PST - ppublish
SO  - Biopharm Drug Dispos. 2019 Feb;40(2):70-80. doi: 10.1002/bdd.2172. Epub 2019 Feb 
      18.