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miR-128 induces pancreas cancer cell apoptosis by targeting MDM4
Hongchao Han1, Lisheng Wang1, Jie Xu2
1Department of General Surgery, The Third People's Hospital, Yancheng, Jiangsu 224000, P.R. China.
Abstract:
MicroRNAs (miRNA/miRs) are small, non-coding RNA molecules (19-25 nucleotides in length), which function to regulate gene expression. It has been reported that miR-128 serves an important role in regulating cancer cell growth; increasing evidence has indicated that the expression of miR-128 is decreased in pancreatic cancer (PC) cells. However, the specific mechanisms of miR-128 in regulating PC cell growth are unclear. In the present study, it was confirmed that the expression of miR-128 was significantly decreased within PC tissues compared with adjacent normal tissues via reverse transcription-quantitative polymerase chain reaction analysis. In addition, miR-128 mimics inhibited PC MIA-PaCa2 cell growth by enhancing cell apoptosis in a caspase-dependent manner. Furthermore, the results of the present study demonstrated that double minute 4 (MDM4) may be a direct target for miR-128 via a dual luciferase report assay; miR-128 may inhibit MDM4 expression, and increase p53 and cleaved caspase-3 protein expression levels. In summary, the present study indicated that miR-128 is downregulated in PC, and it may be a promising target for future PC diagnosis and treatment.
Insights
MicroRNAs (miRNAs) regulate gene expression. This study shows miR-128 is decreased in pancreatic cancer (PC) and inhibits PC cell growth by promoting apoptosis, targeting MDM4.
Area of Science:
- Molecular Biology
- Genetics
- Oncology
Background:
- MicroRNAs (miRNAs) are small, non-coding RNAs regulating gene expression.
- Reduced miR-128 expression is observed in pancreatic cancer (PC).
- The precise role of miR-128 in PC progression remains unclear.
Purpose of the Study:
- To investigate the role and mechanism of miR-128 in pancreatic cancer.
- To confirm miR-128 downregulation in PC tissues.
- To explore miR-128's impact on PC cell growth and apoptosis.
Main Methods:
- Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) to measure miR-128 expression.
- Cell culture (MIA-PaCa2) and treatment with miR-128 mimics.
- Caspase activity assays to assess apoptosis.
- Dual-luciferase reporter assay to identify miR-128 targets.
Main Results:
- miR-128 expression was significantly decreased in PC tissues compared to normal tissues.
- miR-128 mimics inhibited MIA-PaCa2 cell proliferation and induced apoptosis.
- MDM4 was identified as a direct target of miR-128.
- miR-128 upregulation led to decreased MDM4 and increased p53 and cleaved caspase-3 levels.
Conclusions:
- miR-128 is downregulated in pancreatic cancer.
- miR-128 suppresses PC cell growth by targeting MDM4 and promoting apoptosis.
- miR-128 represents a potential diagnostic and therapeutic target for PC.
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