Abstract
Objective To explore the possibility of microRNA miR-31-3p as a biomarker for bone metastasis of non-small-cell lung cancer (NSCLC) and its molecular mechanism to the invasion and metastasis of NSCLC cells. Methods Real-time quantitative PCR (RT-qPCR) was used to detect the expression levels of miR-31-3p and forkhead box 1 (FOXO1) in NSCLC tissues, serum, and cells to analyze the correlation between the expression levels of miR-31-3p and the clinicopathology of NSCLC. After interference with or overexpressing miR-31-3p, NSCLC cell proliferation, apoptosis, invasion ability, and migration ability were detected by MTT, flow cytometry, Transwell, and scratch experiment, respectively. The interaction between miR-31-3p and FOXO1 was further verified by the dual-luciferase reporter experiment. Western blot was performed to detect the protein expression of FOXO1 in tissues and FOXO1, RhoA, p-RhoA, ROCK-2, and p-ROCK-2 in cells. Results In tissues, serum, and NSCLC cell line A549 of the NSCLC patients, the expression of FOXO1 was notably lower, and the miR-31-3p expression was significantly higher. Overexpression of miR-31-3p could distinctly improve the proliferation, invasion, and migration of A549 cells, meanwhile inhibit cell apoptosis, and activate the RhoA/ROCK-2 signaling pathway, while interfering with the expression of miR-31-3p has the opposite function. Besides, bioinformatics analysis and luciferase reporter assay confirmed that FOXO1 was a target gene of miR-31-3p. Overexpressing FOXO1 could inhibit the proliferation and metastasis of A549 cells, but overexpressing miR-31-3p reverses the results. Conclusion This study confirmed that miR-31-3p promotes the proliferation, invasion, and migration of NSCLC cells and inhibits apoptosis through targeted regulating FOXO1 and be a potential therapeutic targets for the treatment of NSCLC.
Highlights
Lung cancer is the most common malignant tumor and ranks the first in the world [1]
The expression of miR-31-3p in Non-small-cell lung cancer (NSCLC) cell A549 was upregulated compared with normal cell 16HBE-T (Figure 1(c))
These results suggest the involvement of miR-31-3p in non-small-cell lung cancer and its bone metastasis
Summary
Lung cancer is the most common malignant tumor and ranks the first in the world [1]. According to the cancerrelated statistics released by the National Cancer Center, lung cancer has the highest morbidity and mortality in China, and about 500,000 people die from it every year [2,3,4]. Non-small-cell lung cancer (NSCLC) is the most common pathological type of lung cancer, accounting for about 85% of cases [5]. Distant metastases often occur to the patient at the advanced stage, leading to a poor prognosis. When the patient is diagnosed with NSCLC, the pathological process has already entered the middle or late stage, missing the best treating period [8], and eventually leading to death.
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