PMID- 33760164
OWN - NLM
STAT- MEDLINE
DCOM- 20210510
LR  - 20210707
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Print)
IS  - 1791-2997 (Linking)
VI  - 23
IP  - 5
DP  - 2021 May
TI  - miR-93-5p promotes insulin resistance to regulate type 2 diabetes progression in 
      HepG2 cells by targeting HGF.
LID - 329 [pii]
LID - 10.3892/mmr.2021.11968 [doi]
AB  - Insulin resistance is a common feature of type 2 diabetes mellitus (T2DM). 
      However, the mechanisms underlying insulin resistance are not completely 
      understood. The present study aimed to investigate the effect of 
      microRNA (miR)‑93‑5p on insulin resistance in T2DM cells. Human hepatocellular 
      carcinoma (HCC; HepG2) cells were cultured in medium with high glucose content 
      (30 mM glucose) to establish an in vitro insulin‑resistant cell model (IR group). 
      Glucose consumption and glycogen synthesis assays were performed to assess 
      glucose consumption and glycogen synthesis, respectively. By performing 
      immunoprecipitation assays, the abundance of the Met‑insulin receptor complex was 
      detected in HepG2 cells. miR‑93‑5p and hepatocyte growth factor (HGF) mRNA 
      expression levels were measured via reverse transcription‑quantitative PCR, and 
      HGF protein expression levels were measured via western blotting. A 
      dual‑luciferase reporter assay was conducted to investigate the interaction 
      between miR‑93‑5p and HGF. Cell Counting Kit‑8, BrdU and caspase‑3 activity 
      assays were performed to evaluate cell viability, proliferation and apoptosis, 
      respectively, in insulin‑resistant HepG2 cells following transfection with small 
      interfering RNA‑HGF, HGF overexpression vector, miR‑93‑5p mimic or miR‑93‑5p 
      inhibitor. The results demonstrated that miR‑93‑5p expression was significantly 
      increased and HGF expression was significantly decreased in HCC tissues isolated 
      from patients with or without T2DM compared with adjacent healthy tissues 
      isolated from patients without T2DM. Compared with the IR group, miR‑93‑5p 
      overexpression significantly increased cell proliferation, glucose consumption 
      and glycogen synthesis, but significantly inhibited apoptosis in 
      insulin‑resistant HepG2 cells. By contrast, compared with the IR group, HGF 
      overexpression significantly inhibited cell proliferation, glucose consumption 
      and glycogen synthesis, but significantly enhanced cell apoptosis in 
      insulin‑resistant HepG2 cells. Following co‑transfection with HGF overexpression 
      vector and miR‑93‑5p mimic, miR‑93‑5p mimic‑mediated induction of HepG2 cell 
      proliferation, glucose consumption and glycogen synthesis in insulin‑resistant 
      HepG2 cells was inhibited. Collectively, the results of the present study 
      indicated that miR‑93‑5p enhanced insulin resistance to regulate T2DM progression 
      in HepG2 cells by targeting HGF.
FAU - Zhou, Man
AU  - Zhou M
AD  - Department of Endocrinology, Wuhan Third Hospital, Wuhan, Hubei 430060, P.R. 
      China.
FAU - Hou, Yilin
AU  - Hou Y
AD  - Department of Endocrinology, Wuhan Third Hospital, Wuhan, Hubei 430060, P.R. 
      China.
FAU - Wu, Jun
AU  - Wu J
AD  - Department of Endocrinology, Wuhan Third Hospital, Wuhan, Hubei 430060, P.R. 
      China.
FAU - Li, Guangli
AU  - Li G
AD  - Department of Endocrinology, Wuhan Third Hospital, Wuhan, Hubei 430060, P.R. 
      China.
FAU - Cao, Ping
AU  - Cao P
AD  - Department of Endocrinology, Wuhan Third Hospital, Wuhan, Hubei 430060, P.R. 
      China.
FAU - Chen, Wan
AU  - Chen W
AD  - Department of Endocrinology, Wuhan Third Hospital, Wuhan, Hubei 430060, P.R. 
      China.
FAU - Hu, Lingli
AU  - Hu L
AD  - Department of Endocrinology, Wuhan Third Hospital, Wuhan, Hubei 430060, P.R. 
      China.
FAU - Gan, Dingyun
AU  - Gan D
AD  - Department of Endocrinology, Wuhan Third Hospital, Wuhan, Hubei 430060, P.R. 
      China.
LA  - eng
PT  - Journal Article
DEP - 20210324
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0 (HGF protein, human)
RN  - 0 (Insulin)
RN  - 0 (MIRN93 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Apoptosis/genetics
MH  - Carcinoma, Hepatocellular/genetics/pathology
MH  - Cell Line, Tumor
MH  - Cell Proliferation/genetics
MH  - Cell Survival/genetics
MH  - Diabetes Mellitus, Type 2/*genetics/metabolism/pathology
MH  - Gene Expression Regulation, Neoplastic
MH  - Glucose/metabolism
MH  - Hep G2 Cells
MH  - Hepatocyte Growth Factor/*genetics
MH  - Humans
MH  - Insulin/genetics
MH  - Insulin Resistance/*genetics
MH  - Liver Neoplasms/genetics/pathology
MH  - MicroRNAs/*genetics
PMC - PMC7974269
OTO - NOTNLM
OT  - microRNA-93-5p
OT  - hepatocyte growth factor
OT  - type 2 diabetes
OT  - insulin resistance
COIS- The authors declare that they have no competing interests.
EDAT- 2021/03/25 06:00
MHDA- 2021/05/11 06:00
PMCR- 2021/03/08
CRDT- 2021/03/24 12:58
PHST- 2020/06/15 00:00 [received]
PHST- 2021/01/04 00:00 [accepted]
PHST- 2021/03/24 12:58 [entrez]
PHST- 2021/03/25 06:00 [pubmed]
PHST- 2021/05/11 06:00 [medline]
PHST- 2021/03/08 00:00 [pmc-release]
AID - 329 [pii]
AID - MMR-0-0-11968 [pii]
AID - 10.3892/mmr.2021.11968 [doi]
PST - ppublish
SO  - Mol Med Rep. 2021 May;23(5):329. doi: 10.3892/mmr.2021.11968. Epub 2021 Mar 24.