PMID- 33993382
OWN - NLM
STAT- MEDLINE
DCOM- 20210917
LR  - 20240102
IS  - 1432-0843 (Electronic)
IS  - 0344-5704 (Linking)
VI  - 88
IP  - 2
DP  - 2021 Aug
TI  - MiRNA-3662 reverses the gemcitabine resistance in pancreatic cancer through 
      regulating the tumor metabolism.
PG  - 343-357
LID - 10.1007/s00280-021-04289-z [doi]
AB  - OBJECTIVES: Gemcitabine (Gem) is one of the most commonly used chemotherapeutic 
      drugs in treating patients with pancreatic ductal adenocarcinoma (PDAC). Acquired 
      drug resistance against Gem presents a major clinical challenge in the 
      chemotherapy of PDAC. It has been shown that miRNA-3662 is lowly expressed and 
      implicated with quantities of biological processes in cancer. However, whether 
      miRNA-3662 regulates chemoresistance in PDAC remains largely unknown. MATERIALS 
      AND METHODS: The level of miRNA-3662 in PDAC tissues was determined by real-time 
      qPCR (RT-qPCR). Functional experiments were used to investigate the biological 
      role of miRNA-3662 on Gem resistance of PDAC in vitro and in vivo. Fluorescence 
      in situ hybridization (FISH), RT-qPCR, western blotting, bioinformatics analysis 
      and luciferase reporter assay were employed to determine the precise regulation 
      mechanisms. RESULTS: In this study, it was investigated that miRNA-3662 was 
      down-regulated in PDAC clinical samples as well as cell lines. Functional assays 
      revealed that miRNA-3662 was sufficient to inhibit Gem resistance in PDAC cells 
      both in vitro and in vivo. Mechanistically, hypoxia-inducible factor 1a (HIF-1a) 
      was one of the transcriptional target of miRNA-3662 and was up-regulated in PDAC 
      samples. Importantly, genetic promoting of HIF-1a largely compromised 
      miR-3662-mediated chemosensitive effects. In addition, miR-3662 could impair the 
      aerobic glycolysis in PDAC cells. CONCLUSIONS: This study sheds light on 
      miRNA-3662 inhibits PDAC cell chemoresistance and aerobic glycolysis through a 
      negative feedback loop with HIF-1a. Therefore, the co-delivery of miR-3662 and 
      Gem could be served as a promising therapeutic regimen for PDAC patients.
FAU - Liu, An
AU  - Liu A
AUID- ORCID: 0000-0002-2160-1222
AD  - Department of Chemistry and Chemical Engineering, Hunan Institute of Science and 
      Technology, Yueyang, 414006, People's Republic of China.
FAU - Zhou, Yonggui
AU  - Zhou Y
AD  - Department of Gastrointestinal Surgery, The First People's Hospital of Yueyang, 
      Yueyang, 414000, People's Republic of China.
FAU - Zhao, Tian
AU  - Zhao T
AD  - Department of Chemistry and Chemical Engineering, Hunan Institute of Science and 
      Technology, Yueyang, 414006, People's Republic of China.
FAU - Tang, Xu
AU  - Tang X
AD  - Department of Intensive Care, The Second People's Hospital of Yueyang, Yueyang, 
      414006, People's Republic of China. muhaiqi2015@126.com.
FAU - Zhou, Binbin
AU  - Zhou B
AD  - Department of Chemistry and Chemical Engineering, Hunan Institute of Science and 
      Technology, Yueyang, 414006, People's Republic of China. 442628565@qq.com.
FAU - Xu, Jia
AU  - Xu J
AD  - Department of Gastrointestinal Surgery, The First People's Hospital of Yueyang, 
      Yueyang, 414000, People's Republic of China. misshartha@qq.com.
LA  - eng
GR  - 2020JJ5221/Natural Science Foundation of Hunan Province/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210515
PL  - Germany
TA  - Cancer Chemother Pharmacol
JT  - Cancer chemotherapy and pharmacology
JID - 7806519
RN  - 0 (MIRN-3662 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0W860991D6 (Deoxycytidine)
RN  - 0 (Gemcitabine)
SB  - IM
MH  - Animals
MH  - Apoptosis/genetics
MH  - Carcinoma, Pancreatic Ductal/drug therapy/genetics
MH  - Cell Line, Tumor
MH  - Deoxycytidine/*analogs & derivatives/pharmacology
MH  - Down-Regulation/genetics
MH  - Drug Resistance, Neoplasm/*genetics
MH  - Gene Expression Regulation, Neoplastic/genetics
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - MicroRNAs/*genetics
MH  - Pancreatic Neoplasms/*drug therapy/*genetics
MH  - Up-Regulation/genetics
MH  - Gemcitabine
OTO - NOTNLM
OT  - Chemoresistance
OT  - HIF-1a
OT  - MiRNA-3662
OT  - Pancreatic adenocarcinoma
EDAT- 2021/05/17 06:00
MHDA- 2021/09/18 06:00
CRDT- 2021/05/16 21:03
PHST- 2021/01/10 00:00 [received]
PHST- 2021/04/22 00:00 [accepted]
PHST- 2021/05/17 06:00 [pubmed]
PHST- 2021/09/18 06:00 [medline]
PHST- 2021/05/16 21:03 [entrez]
AID - 10.1007/s00280-021-04289-z [pii]
AID - 10.1007/s00280-021-04289-z [doi]
PST - ppublish
SO  - Cancer Chemother Pharmacol. 2021 Aug;88(2):343-357. doi: 
      10.1007/s00280-021-04289-z. Epub 2021 May 15.