PMID- 34596215
OWN - NLM
STAT- MEDLINE
DCOM- 20220218
LR  - 20220218
IS  - 1745-7270 (Electronic)
IS  - 1672-9145 (Linking)
VI  - 53
IP  - 11
DP  - 2021 Nov 10
TI  - Syndecan-2, negatively regulated by miR-20b-5p, contributes to 5-fluorouracil 
      resistance of colorectal cancer cells via the JNK/ERK signaling pathway.
PG  - 1547-1557
LID - 10.1093/abbs/gmab124 [doi]
AB  - 5-Fluorouracil (5-FU) resistance has been long considered as an obstacle to the 
      efficacy of chemotherapy in colorectal cancer (CRC). In this study, we 
      demonstrated the role of miR-20b-5p-regulated syndecan-2 (SDC2) in 5-FU 
      resistance of CRC cells. 5-FU-resistant SW480 CRC cells were established by 
      treatment of SW480 cells with stepwise increase of 5-FU concentration. The 
      results showed that SDC2 was expressed significantly higher in SW480/5-FU cells 
      than in SW480/WT cells as revealed by quantitative real-time polymerase chain 
      reaction and western blot analysis. MTT assay and BrdU assay showed that SDC2 
      overexpression led to increased cell survival rate, while SDC2 knockdown reversed 
      the drug resistance of SW480/5-FU cells. Wound healing and transwell invasion 
      assays revealed that knockdown of SDC2 inhibited the migratory and invasive 
      ability of SW480/5-FU cells. Moreover, animal experiments indicated that si-SDC2 
      plays a suppressive role in tumor growth in vivo. We also confirmed that 
      miR-20b-5p interacted with SDC2, which reversed the effect of SDC2 in SW480/5-FU 
      cells via the c-Jun N-terminal kinase (JNK)/extracellular regulated protein 
      kinases (ERK) signaling pathway. These findings showed that JNK/ERK signaling 
      pathway is involved in miR-20b-5p/SDC2 axis-mediated 5-FU resistance in 
      SW480/5-FU cells, indicating that the miR-20b-5p/SDC2 axis is a potential target 
      for reversing 5-FU resistance in CRC.
CI  - (c) The Author(s) 2021. Published by Oxford University Press on behalf of the 
      Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences. All 
      rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
FAU - Hua, Ruheng
AU  - Hua R
AD  - Department of Gastrointestinal Surgery, Affiliated Hospital of Nantong 
      University, Nantong 226021, China.
AD  - Department of General Surgery, Northern Jiangsu People's Hospital, Clinical 
      Medical College, Yangzhou University, Yangzhou 225001, China.
FAU - Zhang, Yan
AU  - Zhang Y
AD  - Department of Chemotherapy, Affiliated Hospital of Nantong University, Nantong 
      226021, China.
FAU - Yan, Xiyue
AU  - Yan X
AD  - Department of Hematology, Northern Jiangsu People's Hospital, Yangzhou 225001, 
      China.
FAU - Tang, Dong
AU  - Tang D
AD  - Department of General Surgery, Northern Jiangsu People's Hospital, Clinical 
      Medical College, Yangzhou University, Yangzhou 225001, China.
FAU - Li, Xiaolong
AU  - Li X
AD  - Department of Gastrointestinal Surgery, Affiliated Hospital of Nantong 
      University, Nantong 226021, China.
FAU - Ni, Qingfeng
AU  - Ni Q
AD  - Department of Gastrointestinal Surgery, Affiliated Hospital of Nantong 
      University, Nantong 226021, China.
FAU - Wang, Daorong
AU  - Wang D
AD  - Department of General Surgery, Northern Jiangsu People's Hospital, Clinical 
      Medical College, Yangzhou University, Yangzhou 225001, China.
FAU - Zhu, Jianwei
AU  - Zhu J
AD  - Department of Gastrointestinal Surgery, Affiliated Hospital of Nantong 
      University, Nantong 226021, China.
LA  - eng
GR  - JC2019074/Social Development Foundation of Nantong city/
GR  - Social Development Foundation of Nantong City/
PT  - Journal Article
PL  - China
TA  - Acta Biochim Biophys Sin (Shanghai)
JT  - Acta biochimica et biophysica Sinica
JID - 101206716
RN  - 0 (ABCB1 protein, human)
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B)
RN  - 0 (Antimetabolites, Antineoplastic)
RN  - 0 (BCL2 protein, human)
RN  - 0 (BIRC5 protein, human)
RN  - 0 (LRP5 protein, human)
RN  - 0 (Low Density Lipoprotein Receptor-Related Protein-5)
RN  - 0 (MIRN20b microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (SDC2 protein, human)
RN  - 0 (Survivin)
RN  - 149769-25-5 (Syndecan-2)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - U3P01618RT (Fluorouracil)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily B/genetics/metabolism
MH  - Animals
MH  - Antimetabolites, Antineoplastic/pharmacology
MH  - Base Pairing
MH  - Cell Line, Tumor
MH  - Cell Movement/drug effects
MH  - Cell Proliferation/drug effects
MH  - Colorectal Neoplasms/drug therapy/*genetics/metabolism/pathology
MH  - Computational Biology/methods
MH  - Drug Resistance, Neoplasm/*genetics
MH  - Extracellular Signal-Regulated MAP Kinases/*genetics/metabolism
MH  - Female
MH  - Fluorouracil/*pharmacology
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Low Density Lipoprotein Receptor-Related Protein-5/genetics/metabolism
MH  - Mice
MH  - Mice, Nude
MH  - MicroRNAs/*genetics/metabolism
MH  - Neoplasm Invasiveness
MH  - Proto-Oncogene Proteins c-bcl-2/genetics/metabolism
MH  - RNA, Small Interfering/genetics/metabolism
MH  - Signal Transduction
MH  - Survivin/genetics/metabolism
MH  - Syndecan-2/antagonists & inhibitors/*genetics/metabolism
MH  - Xenograft Model Antitumor Assays
OTO - NOTNLM
OT  - 5-fluorouracil resistance
OT  - JNK/ERK
OT  - colorectal cancer
OT  - miR-20b-5p
OT  - syndecan-2
EDAT- 2021/10/02 06:00
MHDA- 2022/02/19 06:00
CRDT- 2021/10/01 08:48
PHST- 2021/04/13 00:00 [received]
PHST- 2021/10/02 06:00 [pubmed]
PHST- 2022/02/19 06:00 [medline]
PHST- 2021/10/01 08:48 [entrez]
AID - 6378813 [pii]
AID - 10.1093/abbs/gmab124 [doi]
PST - ppublish
SO  - Acta Biochim Biophys Sin (Shanghai). 2021 Nov 10;53(11):1547-1557. doi: 
      10.1093/abbs/gmab124.