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MIR9-3HG/let-7c-5p/THBS1 axis promotes hepatocellular carcinoma progression
Jinmin Su1, Jiaoling Gu1, Zhizhong Lu2
1Department of Clinical Laboratory, The 966th Hospital of The PLA Joint Logistic Support Forse, Liaoning, 118000, China.
Background:
Long non-coding RNAs (lncRNA) are key regulators in hepatocellular carcinoma (HCC). However, the role of MIR9-3HG in HCC remained unclear.
Objective:
This study investigated the expression, clinical significance, and molecular mechanism of MIR9-3HG in HCC.
Methods:
MIR9-3HG, hsa-let-7c-5p, and THBS1 levels were quantified via RT-qPCR in 179 paired HCC tissues and cell lines. Associations between MIR9-3HG expression and clinicopathological features were analyzed using χ2 test. The prognostic value was assessed using Kaplan-Meier and Cox regression analyses. The biological functions of MIR9-3HG were evaluated through CCK-8, Transwell assays. The competing endogenous RNA (ceRNA) targeting relationship was validated using dual-luciferase reporter.
Results:
MIR9-3HG was significantly upregulated in HCC tissues and cell lines. High MIR9-3HG expression correlated with advanced TNM stage, higher Edmondson-Steiner grade, vascular invasion, and poor overall survival, and was identified as an independent prognostic factor. Hsa-let-7c-5p expression was negatively correlated with MIR9-3HG and THBS1in HCC tissues. In vitro experiments, silencing MIR9-3HG inhibited HCC cell proliferation, migration, and invasion. Luciferase reporter assays demonstrated that MIR9-3HG functioned as a ceRNA to sponge hsa-let-7c-5p. In turn, hsa-let-7c-5p directly targeted and negatively regulated THBS1.
Conclusion:
MIR9-3HG promoted HCC aggressiveness by acting as a ceRNA for hsa-let-7c-5p to upregulate THBS1. These findings highlighted its potential as a prognostic biomarker.
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