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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
Targeting PKCε by miR-143 regulates cell apoptosis in lung cancer
Ni Zhang1, Yunshu Su, Lijun Xu
1Department of Throracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Abstract:
Non-small cell lung cancer (NSCLC) is one of the most common causes for lung cancer and cancer-related death. The imbalance between cell proliferation and apoptosis was suggested to play an important role in cancer pathogenesis and PKCε is one of the widely recognized targets. Here, we demonstrate that miR-143 is aberrantly downregulated in NSCLC tissue and negatively correlates with expression of PKCε. We show that miR-143 specifically targets the 3'-UTR of PKCε and regulates its expression. Treatment with miR-143 inhibitor mimics cell proliferation and apoptosis imbalance in NSCLC, while inhibition of PKCε can reverse it. Our findings suggest that targeting PKCε overexpression in NSCLC should be beneficial for lung cancer therapy.
Insights
MicroRNA-143 (miR-143) is downregulated in non-small cell lung cancer (NSCLC), impacting cell growth and death. Restoring miR-143 or inhibiting PKCε may offer new therapeutic strategies for NSCLC.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related mortality.
- An imbalance between cell proliferation and apoptosis is implicated in NSCLC pathogenesis.
- Protein kinase C epsilon (PKCε) is a known target involved in cancer development.
Purpose of the Study:
- To investigate the role of miR-143 in NSCLC.
- To determine the relationship between miR-143 and PKCε expression in NSCLC.
- To explore the therapeutic potential of targeting the miR-143/PKCε axis in NSCLC.
Main Methods:
- Analysis of miR-143 and PKCε expression in NSCLC tissues.
- Luciferase reporter assays to confirm direct targeting of PKCε by miR-143.
- In vitro experiments using miR-143 inhibitors and PKCε inhibitors in NSCLC models.
Main Results:
- miR-143 was found to be downregulated in NSCLC tissues.
- A negative correlation between miR-143 and PKCε expression was observed.
- miR-143 directly targets and regulates PKCε expression.
- Inhibition of miR-143 promoted NSCLC cell proliferation and inhibited apoptosis.
- Inhibition of PKCε reversed the effects induced by miR-143 inhibition.
Conclusions:
- miR-143 plays a tumor-suppressive role in NSCLC by regulating PKCε.
- Targeting PKCε overexpression presents a potential therapeutic strategy for NSCLC.
