PMID- 35339472
OWN - NLM
STAT- MEDLINE
DCOM- 20220413
LR  - 20220506
IS  - 1090-2422 (Electronic)
IS  - 0014-4827 (Linking)
VI  - 415
IP  - 1
DP  - 2022 Jun 1
TI  - Significance of a tumor microenvironment-mediated P65-miR-30a-5p-BCL2L11 
      amplification loop in multiple myeloma.
PG  - 113113
LID - S0014-4827(22)00106-9 [pii]
LID - 10.1016/j.yexcr.2022.113113 [doi]
AB  - Despite significant progress in the treatment of myeloma, multiple myeloma (MM) 
      remains an incurable hematological malignancy due to cell adhesion-mediated drug 
      resistance (CAM-DR) phenotype. However, data on the molecular mechanisms 
      underlying the CAM-DR remains scanty. Here, we identified a miRNA-mRNA regulatory 
      network in myeloma cells that are directly adherent to bone marrow stromal cells 
      (BMSCs). Our data showed that the BMSCs up-regulated miR-30a-5p and 
      down-regulated BCL2L11 at both mRNA and protein level in the myeloma cells. 
      Besides, luciferase reporter genes demonstrated direct interaction between 
      miR-30a-5p and BCL2L11 gene. Moreover, the BMSCs activated NF-KappaB signaling 
      pathway in myeloma cells and the NF-kappaB P65 was shown to directly bind the 
      miR-30a-5p promoter region. Moreover, suppression of the miR-30a-5p or 
      upregulation of the BCL2L11 promoted apoptosis of the myeloma cells independent 
      of the BMSCs, thus suggesting clinical significance of miR-30a-5p inhibitor and 
      PLBCL2L11 plasmid in CAM-DR. Together, our data demonstrated the role of 
      P65-miR-30a-5p-BCL2L11 loop in CAM-DR myeloma cells. These findings give new 
      insights into the role of tumor microenvironment in the treatment of patients 
      with myeloma.
CI  - Copyright (c) 2022 Elsevier Inc. All rights reserved.
FAU - Xie, Lingling
AU  - Xie L
AD  - Department of Laboratory Medicine, Affiliated Hospital of Nantong University, 
      Nantong, 226001, China. Electronic address: xll19882021@163.com.
FAU - Wei, Jinhong
AU  - Wei J
AD  - School of Basic Medical Sciences, Southwest Medical University, Luzhou, 646000, 
      China. Electronic address: 375668996@qq.com.
FAU - Gao, Zhihua
AU  - Gao Z
AD  - Department of Laboratory Medicine, Affiliated Hospital of Nantong University, 
      Nantong, 226001, China.
FAU - Huang, Hongming
AU  - Huang H
AD  - Department of Hematology, Affiliated Hospital of Nantong University, Nantong, 
      226001, China.
FAU - Ju, Shaoqing
AU  - Ju S
AD  - Department of Laboratory Medicine, Affiliated Hospital of Nantong University, 
      Nantong, 226001, China.
FAU - Wang, Xudong
AU  - Wang X
AD  - Department of Laboratory Medicine, Affiliated Hospital of Nantong University, 
      Nantong, 226001, China.
LA  - eng
PT  - Journal Article
DEP - 20220323
PL  - United States
TA  - Exp Cell Res
JT  - Experimental cell research
JID - 0373226
RN  - 0 (BCL2L11 protein, human)
RN  - 0 (Bcl-2-Like Protein 11)
RN  - 0 (MicroRNAs)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Bcl-2-Like Protein 11/metabolism
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Gene Expression Regulation, Neoplastic/genetics
MH  - Humans
MH  - *MicroRNAs/genetics/metabolism
MH  - *Multiple Myeloma/genetics
MH  - NF-kappa B/metabolism
MH  - RNA, Messenger
MH  - Tumor Microenvironment/genetics
OTO - NOTNLM
OT  - Cell adhesion-mediated drug resistance
OT  - NF-KappaB signaling pathway
OT  - Tumor microenvironment
OT  - miRNA-mRNA regulatory network
OT  - microRNAs
EDAT- 2022/03/28 06:00
MHDA- 2022/04/14 06:00
CRDT- 2022/03/27 20:20
PHST- 2021/09/25 00:00 [received]
PHST- 2022/03/20 00:00 [revised]
PHST- 2022/03/21 00:00 [accepted]
PHST- 2022/03/28 06:00 [pubmed]
PHST- 2022/04/14 06:00 [medline]
PHST- 2022/03/27 20:20 [entrez]
AID - S0014-4827(22)00106-9 [pii]
AID - 10.1016/j.yexcr.2022.113113 [doi]
PST - ppublish
SO  - Exp Cell Res. 2022 Jun 1;415(1):113113. doi: 10.1016/j.yexcr.2022.113113. Epub 
      2022 Mar 23.