The long noncoding RNA XIST protects cardiomyocyte hypertrophy by targeting miR-330-3p
Yuewu Chen1, Xianxia Liu1, Lei Chen1
1Department of Cardiovascular Medicine, The Second Affiliated Hospital of Hainan Medical University, Haikou, 570100, Hainan Province, China.
Abstract:
Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are implicated in numerous kinds of cardiovascular diseases, and their vital role in regulating cardiac hypertrophy still needs to be explored. In this study, we demonstrated that lncRNA X-inactive specific transcript (XIST) was upregulated in hypertrophic cardiac of mice and phenylephrine (PE)-treated cardiomyocytes. Next, we observed that inhibition of XIST induced hypertrophic response of cardiomyocyte and overexpression of XIST attenuated cardiomyocyte hypertrophy induced by PE. Furthermore, through online predictive tools and functional experiments, we demonstrated that XIST and S100B were targets of miR-330-3p. XIST and miR-330-3p suppressed each other in a reciprocal way in cardiomyocytes. Additionally, XIST promoted S100B expression through harboring the complementary binding sites with miR-330-3p, eventually prevented cardiac hypertrophy. In conclusion, our findings revealed a novel molecular mechanism that XIST/miR-330-3p/S100B pathway modulates the progression of cardiomyocyte hypertrophy.
Insights
Long non-coding RNA XIST and microRNA-330-3p regulate cardiac hypertrophy. XIST promotes S100B expression, preventing hypertrophy via the XIST/miR-330-3p/S100B pathway.
Area of Science:
- Molecular Biology
- Cardiovascular Research
- Gene Regulation
Background:
- Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) play roles in cardiovascular diseases.
- The specific function of lncRNA XIST in cardiac hypertrophy requires further investigation.
Purpose of the Study:
- To elucidate the role of lncRNA XIST in cardiomyocyte hypertrophy.
- To identify the molecular mechanism involving XIST, miR-330-3p, and S100B in cardiac hypertrophy.
Main Methods:
- Quantitative real-time PCR to measure gene expression.
- In vitro gain- and loss-of-function studies in cardiomyocytes.
- Bioinformatic analysis and luciferase reporter assays to confirm target interactions.
Main Results:
- XIST was upregulated in hypertrophic cardiac tissue and cardiomyocytes.
- XIST inhibition exacerbated hypertrophy, while XIST overexpression attenuated it.
- XIST and miR-330-3p exhibited reciprocal suppression.
- XIST promoted S100B expression by sponging miR-330-3p, thereby preventing cardiac hypertrophy.
Conclusions:
- A novel XIST/miR-330-3p/S100B pathway was identified that modulates cardiomyocyte hypertrophy.
- This pathway represents a potential therapeutic target for cardiovascular diseases involving cardiac hypertrophy.
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