MicroRNA-652-3p Promotes Non-small Cell Lung Cancer Proliferation、Migration And Invasion By Suppressing Lgl1 Expression

Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer death in men and women worldwide. An estimated 1.8 million new lung cancer cases occurred worldwide in 2012, accounting for approximately 13% of all cancer diagnoses. The overall 5-year survival rate for lung cancer is only 17.1%, and it declines to 3.6% for those with stage Ⅳ disease. Tumor distant metastasesand late diagnosis of lung cancer are obstacles for survival. Thus, diagnosis at an early stage, understanding the molecular mechanisms and identifying novel targets are urgently needed for the treatment of NSCLC.MicroRNAs are approximately 19-24 nucleotide non-coding RNAs that regulate gene expression by complementarily binding to the 3’UTR sequence of their target mRNA, thus leading to mRNA degradation or translational repression. MicroRNAs have also been implicated in transcriptional regulation by targeting promoter elements, a phenomenon known as RNA activation (RNAa). MicroRNAs can function as either oncogenes or tumor suppressors involved in the initiation and progression of different types of cancer. A number of miRNAs have been reported to have altered expression and to be involved in the carcinogenesis and development of NSCLC.Our previous study has found that miR-652-3p was markedly upregulated in the serum of patients with NSCLC and suggested that miR-652-3p was a potential biomarker for the early diagnosis of NSCLC. In this study, we detected the expression of miR-652-3p in NSCLC tumor tissues and cell lines and investigated the effect of miR-652-3p on the proliferation and metastasis of NSCLC cells. Our results showed that the expression of miR-652-3p was significantly upregulated in tumor tissues of 50 patients with NSCLC and 6 NSCLC cell lines, and it was significantly higher in patients with positive lymph node metastasis, advanced TNM stage and poor prognosis. Using functional analyses by overexpressing or suppressing miR-652-3p in NSCLC cells, we demonstrated that miR-652-3p promoted cell proliferation, migration, invasion and inhibited cell apoptosis. Moreover, the lethal giant larvae homolog 1 (Lgl1) was identified as a direct and functional target of miR-652-3p. Overexpression or knockdown of miR-652-3p led to decreased or increased expression of Lgl1 protein, and the binding site mutation of LLGL1 3’UTR abrogated the responsiveness of the luciferase reporters to miR-652-3p.Overexpression of Lgl1 partially attenuated the function of miR-652-3p. Besides, there is a negative correlation between miR-652-3p and Lgl1 expression level in 50 NSCLC samples.In conclusion, we provided clear evidence that miR-652-3p is frequently upregulated in NSCLC tissues, and miR-652-3p executes a tumor-promoter function in NSCLC. We also revealed a new regulatory mechanism of Lgl1 in NSCLC, as it is downregulated by miR-652-3p through direct targeting of its 3’UTR.