MicroRNA-204 inhibits the proliferation, migration and invasion of human lung cancer cells by targeting PCNA-1 and inhibits tumor growth in vivo

Lung cancer accounts for similar to 20% of the total cancer-associated mortalities worldwide. Lung cancer is often diagnosed at advanced stages and is therefore difficult to treat. The biomarkers for diagnosis of lung cancer are limited and unreliable. In addition, the lack of availability of efficient chemotherapeutic agents and targets has resulted in limitations in the successful treatment of lung cancer. Previously, microRNAs (miRNA/miR) have been implicated in the onset and development of several types of cancer. The expression of miRNAs is often dysregulated in cancer cells; therefore, they are considered important therapeutic targets and agents. The present study examined the expression of miR-204 in 4 different lung cancer cell lines and 1 normal cell line. The results revealed that miR-204 was significantly downregulated (4-8-fold) in all the cancer cell lines (P<0.05). Overexpression of miR-204 in A549 lung cancer cells inhibited the proliferative, migratory and invasive capabilities of the lung cancer cells. Furthermore, miR-204 overexpression also induced apoptosis in the A549 lung cancer cells. Bioinformatics analysis revealed proliferating cell nuclear antigen 1 (PCNA-1) to be a potential target of miR-204. The reverse transcription quantitative polymerase chain reaction analysis revealed that PCNA-1 was significantly upregulated (up to 5-fold) in the lung cancer cells (P<0.05), and the over-expression of miR-204 caused the downregulation of PCNA-1 in A549 lung cancer cells. Silencing of PCNA-1 in A549 cells exerted similar effects to that of miR-204 overexpression on the proliferative, migratory and invasive capabilities of A549 lung cancer cells. Additionally, the suppression of miR-204 in A549 cells transfected with Si-PCNA-1 did not rescue the effects of PCNA-1 silencing on cell proliferation, migration or invasion. Conversely, the overexpression of PCNA-1 in A549 cells transfected with miR-204 mimics promoted the proliferation, migration and invasion of lung cancer cells. Furthermore, overexpression of miR-204 in xenograft tumors significantly inhibited their growth. Taken together, these results indicated that miR-204 regulates the proliferative, migratory and invasive capabilities of lung cancer cells by targeting PCNA-1.