PMID- 36789695
OWN - NLM
STAT- MEDLINE
DCOM- 20230216
LR  - 20240102
IS  - 1745-7270 (Electronic)
IS  - 1672-9145 (Print)
IS  - 1672-9145 (Linking)
VI  - 54
IP  - 12
DP  - 2022 Dec 25
TI  - DSCR9/miR-21-5p axis inhibits pancreatic cancer proliferation and resistance to 
      gemcitabine via BTG2 signaling.
PG  - 1775-1788
LID - 10.3724/abbs.2022194 [doi]
AB  - The outcome of pancreatic adenocarcinoma (PAAD) patients is poor, given 
      resistance to gemcitabine. Long noncoding RNA (lncRNA) has been implicated in the 
      carcinogenesis of pancreatic cancer; however, its function and mechanism in PAAD 
      resistance to gemcitabine (GEM) are yet unknown. Herein, we demonstrate that 
      lncRNA DSCR9 is significantly reduced in PAAD in vitro and in vivo. CCK-8, BrdU 
      and flow cytometry assays show that overexpression of DSCR9 markedly suppresses 
      pancreatic cancer cell proliferation and invasion, and promotes apoptosis under 
      gemcitabine treatment. BTG2 acts as a tumor suppressor by reducing the 
      proliferation and invasion of pancreatic cancer cells and increasing 
      gemcitabine-induced apoptosis. Immunofluorescence (IF) staining combined with 
      fluorescence in situ hybridization (FISH) of pancreatic cancer tissues shows that 
      DSCR9 and BTG2 are both increased in pancreatic cancer tissues. Luciferase assay 
      shows that miR-21-5p simultaneously binds to DSCR9 and 3'UTR of BTG2; DSCR9 
      relieves miR-21-5p-induced inhibition of BTG2 by competing with BTG2 for 
      miR-21-5p binding. Overexpression of miR-21-5p enhances the invasiveness of 
      pancreatic cancer cells by promoting cancer cell proliferation and invasion and 
      attenuating gemcitabine-induced apoptosis. Overexpression of miR-21-5p attenuates 
      the effect of DSCR9 overexpression on BTG2 expression and invasiveness of 
      pancreatic cancer cells. Finally, miR-21-5p expression is increased, while BTG2 
      expression is decreased in pancreatic cancer tissues. miR-21-5p is negatively 
      correlated with DSCR9 and BTG2. In conclusion, the DSCR9/miR-21-5p/BTG2 axis 
      modulates pancreatic cancer proliferation, invasion, and gemcitabine resistance.
FAU - Huang, Hui
AU  - Huang H
AD  - Department of Hepatopancreatobiliary Surgery, Third Xiangya Hospital, Central 
      South University, Changsha 410013, China.
FAU - Li, Xia
AU  - Li X
AD  - Department of Endocrinology, Third Xiangya Hospital, Central South University, 
      Changsha 410013, China.
FAU - Zhang, Xianlin
AU  - Zhang X
AD  - Department of General Surgery, Affiliated Renhe Hospital of China Three Gorges 
      University, Yichang 443001, China.
FAU - Li, Zhiqiang
AU  - Li Z
AD  - Department of Hepatopancreatobiliary Surgery, Third Xiangya Hospital, Central 
      South University, Changsha 410013, China.
FAU - Han, Duo
AU  - Han D
AD  - Department of Hepatopancreatobiliary Surgery, Third Xiangya Hospital, Central 
      South University, Changsha 410013, China.
FAU - Gao, Wenzhe
AU  - Gao W
AD  - Department of Hepatopancreatobiliary Surgery, Third Xiangya Hospital, Central 
      South University, Changsha 410013, China.
FAU - Liu, Ling
AU  - Liu L
AD  - Department of Cardiology, Second People's Hospital of Hunan Province, Hunan 
      University of Chinese Medicine, Changsha 410007, China.
FAU - Peng, Cheng
AU  - Peng C
AD  - Department of Hepatopancreatobiliary Surgery, Third Xiangya Hospital, Central 
      South University, Changsha 410013, China.
FAU - Zhu, Hongwei
AU  - Zhu H
AD  - Department of Hepatopancreatobiliary Surgery, Third Xiangya Hospital, Central 
      South University, Changsha 410013, China.
FAU - Yu, Xiao
AU  - Yu X
AD  - Department of Hepatopancreatobiliary Surgery, Third Xiangya Hospital, Central 
      South University, Changsha 410013, China.
LA  - eng
PT  - Journal Article
PL  - China
TA  - Acta Biochim Biophys Sin (Shanghai)
JT  - Acta biochimica et biophysica Sinica
JID - 101206716
RN  - 0 (Gemcitabine)
RN  - 0 (MicroRNAs)
RN  - 0 (RNA, Long Noncoding)
RN  - 141490-22-4 (BTG2 protein, human)
RN  - 0 (Immediate-Early Proteins)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 0 (MIRN21 microRNA, human)
SB  - IM
MH  - Humans
MH  - Gemcitabine
MH  - *MicroRNAs/metabolism
MH  - *Pancreatic Neoplasms/drug therapy/genetics/metabolism
MH  - *Adenocarcinoma/drug therapy/genetics
MH  - *RNA, Long Noncoding/genetics/metabolism
MH  - In Situ Hybridization, Fluorescence
MH  - Cell Proliferation/genetics
MH  - Cell Line, Tumor
MH  - Gene Expression Regulation, Neoplastic
MH  - Cell Movement/genetics
MH  - Apoptosis
MH  - *Immediate-Early Proteins/genetics
MH  - Tumor Suppressor Proteins/genetics/metabolism
PMC - PMC10157615
OTO - NOTNLM
OT  - BTG2
OT  - gemcitabine resistance
OT  - lncRNA DSCR9
OT  - miR-21-5p
OT  - pancreatic cancer
OT  - proliferation
COIS- The authors declare that they have no conflict of interest.
EDAT- 2023/02/16 06:00
MHDA- 2023/02/17 06:00
PMCR- 2022/12/26
CRDT- 2023/02/15 04:13
PHST- 2023/02/15 04:13 [entrez]
PHST- 2023/02/16 06:00 [pubmed]
PHST- 2023/02/17 06:00 [medline]
PHST- 2022/12/26 00:00 [pmc-release]
AID - 10.3724/abbs.2022194 [doi]
PST - ppublish
SO  - Acta Biochim Biophys Sin (Shanghai). 2022 Dec 25;54(12):1775-1788. doi: 
      10.3724/abbs.2022194.