miR-383 inhibits hepatocellular carcinoma cell proliferation via targeting APRIL
Lin Chen1, Haitao Guan1, Chunyan Gu1
1Department of Gastroenterology and Clinical Laboratory, The Third People's Hospital of Nantong City, Jiangsu, 226006, China.
Abstract:
Mounting evidence has shown that microRNAs (miRNAs), a class of small non-coding RNAs, are frequently deregulated in human malignancies and have pivotal roles in diverse biological processes including cancer cell proliferation. Herein, we investigated the expression pattern of miR-383 in 64 hepatocellular carcinoma (HCC) tissues and 4 HCC cell lines and found that miR-383 was downregulated in HCC tissues and cell lines. Moreover, miR-383 expression in HCC was significantly correlated with tumor size and tumor-node-metastasis (TNM) stage. Kaplan-Meier analysis showed that decreased miR-383 expression was associated with poor overall survival of HCC patients. In addition, Cox regression analysis indicated that miR-383 was an independent prognostic factor for HCC patients. Then, functional studies demonstrated that ectopic miR-383 expression could significantly suppress the in vitro proliferation of HCC cells, as well as induce cell cycle arrest and cell apoptosis. Luciferase reporter assay further identified that a proliferation-inducing ligand (APRIL), a member in the tumor necrosis factor (TNF) superfamily, was a novel target gene for miR-383. Subsequent investigation revealed that miR-383 expression was inversely correlated with APRIL messenger RNA (mRNA) expression in HCC tissues. Besides, recombinant human APRIL (rhAPRIL) could rescue HCC cell proliferation inhibited by miR-383. Taken together, our present study provided the first evidence that miR-383 was decreased in HCC and associated with tumor progression and prognosis of HCC patients. Furthermore, our findings confirmed that miR-383 might inhibit HCC cell proliferation partially via downregulating APRIL expression. Thus, this study might provide a promising strategy by targeting with the miR-383-APRIL axis in the treatment of HCC.
Insights
MicroRNA-383 (miR-383) is downregulated in hepatocellular carcinoma (HCC), correlating with poor prognosis. Restoring miR-383 suppresses HCC cell proliferation by targeting APRIL, suggesting a potential therapeutic strategy.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- MicroRNAs (miRNAs) are small non-coding RNAs involved in gene regulation.
- Dysregulation of miRNAs is common in human cancers, including hepatocellular carcinoma (HCC).
- miRNAs play critical roles in cancer cell proliferation and progression.
Purpose of the Study:
- To investigate the expression pattern of miR-383 in HCC.
- To determine the correlation between miR-383 expression and HCC patient prognosis.
- To elucidate the functional role of miR-383 in HCC cell proliferation and identify its target genes.
Main Methods:
- Quantitative real-time PCR to assess miR-383 expression in HCC tissues and cell lines.
- Kaplan-Meier analysis and Cox regression to evaluate prognostic significance.
- In vitro functional assays (cell proliferation, cell cycle, apoptosis) to study miR-383 effects.
- Luciferase reporter assay to identify miR-383 targets.
- Western blot and rescue experiments to validate the miR-383-APRIL interaction.
Main Results:
- miR-383 was significantly downregulated in HCC tissues and cell lines.
- Lower miR-383 expression correlated with larger tumor size, advanced TNM stage, and poorer patient survival.
- Ectopic miR-383 expression inhibited HCC cell proliferation, induced cell cycle arrest, and promoted apoptosis.
- APRIL (a proliferation-inducing ligand) was identified as a direct target of miR-383.
- APRIL overexpression rescued the anti-proliferative effect of miR-383 in HCC cells.
Conclusions:
- miR-383 is a tumor suppressor in HCC, with its downregulation associated with tumor progression and poor prognosis.
- miR-383 inhibits HCC cell proliferation, at least partially, by downregulating APRIL expression.
- The miR-383-APRIL axis represents a potential therapeutic target for HCC treatment.
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