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
;
Liying SONG
2
;
Zuojun LI
2
;
Peipei MENG
3
;
Shanru ZUO
2
;
Shikun LIU
4
Author Information
1. Department of Pharmacy, Third Xiangya Hospital, Central South University, Changsha 410013. Fangweijin03@126.com.
2. Department of Pharmacy, Third Xiangya Hospital, Central South University, Changsha 410013.
3. Department of Pharmacy, Women and Children's Health Care Hospital of Linyi, Linyi Shandong 276000, China.
4. Department of Pharmacy, Third Xiangya Hospital, Central South University, Changsha 410013. L8618496@126.com.
- 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.
