Abstract
PKCα (protein kinase C alpha, PRKCA) is an important protein involved in several steps of signaling pathways in lung cancer, and microRNAs (miRNAs) have also been shown to participate in lung carcinogenesis. However, it is not clear how PKCα and miRNAs are correlated in the disease. In this report, we aimed to identify novel miRNAs that target PKCα and to study their biological function. Using bioinformatics analysis, we predicted one novel candidate, miR-203, and found differential expression patterns of miR-203 and PKCα in human lung cancer tissues. Moreover, we experimentally validated miR-203 as a direct regulator of PKCα. Finally, we demonstrated that the targeting of PKCα by miR-203 played a critical role in regulating cell proliferation, apoptosis and migration in lung cancer cells. In summary, this study identifies a novel miRNA that targets PKCα and illustrates that the downregulation of PKCα by miR-203 modulates biological processes in lung cancer cells.
Highlights
Lung cancer is the leading cause of cancer-related deaths worldwide, and non–small cell lung cancer (NSCLC) accounts for approximately 80% of all cases [1]
Staurosporine, a potent Protein kinase C (PKC) inhibitor, controls cell adhesion, mobility, and invasion of A549 cells [10]; IL1-beta induces the expression of urokinase plasminogen activator via PKCα, which leads to the migration of A549 NSCLC cells [11]
Using quantitative real-time PCR analysis, we demonstrated that the expression of miR-203 was significantly lower in human lung cancer tissues than in the adjacent normal tissues (Figure 2A); in contrast, PKCα mRNA expression was noticeably higher in cancer cells (Figure 2B)
Summary
Lung cancer is the leading cause of cancer-related deaths worldwide, and non–small cell lung cancer (NSCLC) accounts for approximately 80% of all cases [1]. Protein kinase C (PKC) is a serine/threonine kinase that plays a key role in several signal transduction pathways, including those involved in cellular proliferation, differentiation, and apoptosis [3,4,5]. PKC, including PKCα (PRKCA), plays a part in lung cancer. There have been several reports on the role of PKCα in cellular proliferation, apoptosis and the migration of lung cancer cells. The suppression of PKCα enhances the cytotoxicity and mutagenicity of lead acetate (Pb)-treated CL3 human lung cancer cells [9]. Staurosporine, a potent PKC inhibitor, controls cell adhesion, mobility, and invasion of A549 cells [10]; IL1-beta induces the expression of urokinase plasminogen activator (uPA) via PKCα, which leads to the migration of A549 NSCLC cells [11]
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