Effect of miRNA-200b on the proliferation of liver cancer cells via targeting SMYD2/p53 signaling pathway.
10.11817/j.issn.1672-7347.2022.210521
- Author:
Weijin FANG
1
,
2
,
3
;
Liying SONG
1
;
Zuojun LI
1
;
Peipei MENG
4
;
Shanru ZUO
1
;
Shikun LIU
1
,
3
,
5
Author Information
1. Department of Pharmacy, Third Xiangya Hospital, Central South University, Changsha
2. Fangweijin03@
3. com.
4. Department of Pharmacy, Women and Children's Health Care Hospital of Linyi, Linyi Shandong 276000, China.
5. L8618496@
- Publication Type:Journal Article
- Keywords:
CyclinE1;
SET and MYND domain-containing protein 2;
hepatocellular carcinoma;
miR-200b;
p53
- MeSH:
Humans;
Carcinoma, Hepatocellular/pathology*;
Tumor Suppressor Protein p53/metabolism*;
MicroRNAs/metabolism*;
Cell Line, Tumor;
Signal Transduction;
Liver Neoplasms/pathology*;
Cell Proliferation/genetics*;
Histone-Lysine N-Methyltransferase/metabolism*
- From:
Journal of Central South University(Medical Sciences)
2022;47(10):1303-1314
- CountryChina
- Language:English
-
Abstract:
OBJECTIVES:Our previous study has verified that high level of SET and MYND domain-containing protein 2 (SMYD2) plays an important role in acquiring aggressive ability for liver cancer cells in hepatocellular carcinoma. MiR-200b as a tumor suppressor gene involves in a variety of cancers. This study aims to investigate the correlation between miR-200b and SMYD2 in hepatocellular carcinoma and the underlying mechanism.
METHODS:Firstly, the levels of SMYD2 and miR-200b in hepatocellular carcinoma tissues and matched adjacent non-tumor liver tissues were tested with real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. Secondly, we evaluated the interaction between miR-200b and SMYD2 using dual-luciferase reporter assay. Thirdly, we elucidated the effect of miR-200b on SMYD2 and its downstream targets p53/CyclinE1. Finally, we silenced SMYD2 in hepatocellular carcinoma cell lines to investigate its effect on tumor proliferation and cell cycle progression, and further confirmed the correlation among SMYD2 and p53/CyclinE1.
RESULTS:Compared with the matched adjacent non-tumor liver tissues, miR-200b was obviously decreased, and SMYD2 was significantly increased in hepatocellular carcinoma (both P<0.05). Spearman's rank correlation revealed that miR-200b expression was negatively correlated with SMYD2 (P<0.01). Computer algorithm and dual-luciferase reporter assay revealed that miR-200b directly targeted and suppressed SMYD2 in HEK 293T cells. The down-regulated miR-200b expression promoted hepatoma cell proliferation (P<0.05) and increased SMYD2 expression(P<0.01), while the up-regulated expression of miR-200b had an opposite effect. The knockdown of SMYD2 suppressed the proliferation of MHCC-97L cells (P<0.01), down-regulated CyclinE1, and up-regulated p53 expression (both P<0.05).
CONCLUSIONS:MiR-200b is involved in hepatocellular carcinoma progression via targeting SMYD2 and regulating SMYD2/p53/CyclinE1 signaling pathway and may be used as a potential target for hepatocellular carcinoma treatment.
