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Long non-coding RNA muskelin 1 antisense RNA as a potential therapeutic target in hepatocellular carcinoma treatment
Xijun Chen1, Qing Ye1, Zhigao Chen1
1The Third Clinical Medical College, Fujian Medical University, Fuzhou, Fujian, China.
Abstract:
Long non-coding RNAs are essential to hepatocellular carcinoma (HCC) development, progression, and incidence of drug resistance. However, the biological significance of long non-coding RNA muskelin 1 antisense RNA (MKLN1-AS) remains poorly characterized. In this study, we observed noticeable increased levels of MKLN1-AS in HCC tissues. This upregulation of MKLN1-AS was clinically associated with vascular invasion and decreased disease-free survival and overall survival of patients with HCC. Functionally, MKLN1-AS-knockdown dramatically suppressed the metastasis and growth of HCC cells in vitro and in vivo. Additionally, the knockdown of MKLN1-AS augmented the pro-apoptosis effect of lenvatinib. Taken together, our findings indicate that MKLN1-AS may be exploited as a potential prognostic predictor and therapeutic target for HCC treatment.
Insights
Long non-coding RNA muskelin 1 antisense RNA (MKLN1-AS) is upregulated in hepatocellular carcinoma (HCC), correlating with poor patient survival. Reducing MKLN1-AS inhibits HCC growth and metastasis, suggesting it as a therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Long non-coding RNAs (lncRNAs) play critical roles in hepatocellular carcinoma (HCC) pathogenesis, including tumor development, progression, and drug resistance.
- The specific function and clinical significance of the lncRNA muskelin 1 antisense RNA (MKLN1-AS) in HCC remain largely unknown.
Purpose of the Study:
- To investigate the biological role and clinical relevance of MKLN1-AS in hepatocellular carcinoma.
- To evaluate MKLN1-AS as a potential prognostic biomarker and therapeutic target for HCC.
Main Methods:
- Quantitative real-time PCR was used to measure MKLN1-AS expression levels in HCC tissues.
- Statistical analysis correlated MKLN1-AS expression with clinical parameters, including vascular invasion and patient survival.
- Functional studies involved MKLN1-AS knockdown in HCC cell lines and in vivo models to assess effects on cell growth and metastasis.
- The impact of MKLN1-AS knockdown on lenvatinib-induced apoptosis was examined.
Main Results:
- MKLN1-AS expression was significantly increased in HCC tissues compared to normal tissues.
- Elevated MKLN1-AS levels were associated with vascular invasion and poorer disease-free and overall survival in HCC patients.
- Knockdown of MKLN1-AS suppressed HCC cell proliferation and metastasis both in vitro and in vivo.
- Reducing MKLN1-AS expression enhanced the pro-apoptotic effects of lenvatinib in HCC cells.
Conclusions:
- MKLN1-AS is upregulated in hepatocellular carcinoma and serves as a potential prognostic indicator for patient outcomes.
- MKLN1-AS promotes HCC progression and metastasis, highlighting its role as a therapeutic target.
- Targeting MKLN1-AS may represent a novel strategy for improving HCC treatment efficacy, potentially in combination with existing therapies like lenvatinib.
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