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. 2020 May 15:13:4229-4237.
doi: 10.2147/OTT.S243221. eCollection 2020.

MicroRNA-374b-5p Functions as a Tumor Suppressor in Non-Small Cell Lung Cancer by Targeting FOXP1 and Predicts Prognosis of Cancer Patients

Jianzhao Li  1 , Xinfang Zhang  2 , Jiaying Tang  3 , Cuixue Gong  4
Affiliations

MicroRNA-374b-5p Functions as a Tumor Suppressor in Non-Small Cell Lung Cancer by Targeting FOXP1 and Predicts Prognosis of Cancer Patients

Jianzhao Li et al. Onco Targets Ther. .

Abstract

Background: Lung cancer remains the most frequent malignancy worldwide with increasing morbidity and mortality. This study aimed to assess the expression of microRNA-374b-5p (miR-374b-5p) in tissues and cell lines of non-small cell lung cancer (NSCLC) and to evaluate the prognostic value of miR-374b-5p as well as its biological function in tumor progression.

Materials and methods: Expression of miR-374b-5p in NSCLC patients and cells was estimated using quantitative real-time PCR. The prognostic value of miR-374b-5p was evaluated using Kaplan-Meier method and Cox regression analysis. Gain-of-function and loss-of-function cell experiments were performed to examine the effects of miR-374b-5p on NSCLC cell proliferation, migration and invasion. A luciferase activity assay was used to confirm the target gene of miR-374b-5p.

Results: miR-374b-5p expression levels were decreased in tumorous tissues and cell lines compared with the normal tissues or cells (P < 0.05). The expression of miR-374b-5p was associated with the patients' tumor size, lymph node metastasis and TNM stage (all P < 0.05). Patients with low miR-374b-5p expression have a shorter survival time (log-rank P = 0.001), and the downregulated expression of miR-374b-5p was determined to be an independent prognostic indicator of NSCLC. In NSCLC cells, the overexpression of miR-374b-5p could inhibit NSCLC cell proliferation, migration and invasion and could directly target FOXP1.

Conclusion: This study found that the decreased miR-374b-5p predicts poor prognosis of NSCLC, and the upregulation of miR-374b-5p can inhibit NSCLC cell proliferation, migration and invasion. The data obtained from this study provide a novel candidate prognostic biomarker and a potential therapeutic target for NSCLC.

Keywords: invasion; microRNA-374b-5p; migration; non-small cell lung cancer; prognosis; proliferation.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Expression of miR-374b-5p in NSCLC. (A) Expression of miR-374b-5p in the tissue samples collected from NSCLC patients. (B) Different expression levels of miR-374b-5p in four NSCLC cell lines. ***P < 0.001.
Figure 2
Figure 2
Kaplan-Meier survival curves for NSCLC patients based on different miR-374b-5p expressions. Log-rank P =0.001.
Figure 3
Figure 3
Effects of miR-374b-5p on cell proliferation, migration and invasion of A549 and H460 cells. (A) Cell transfection efficiency examination results. (B) Inhibiting effect of miR-374b-5p on NSCLC cell proliferation. (C and D) miR-374b-5p suppressed NSCLC cell migration (C) and invasion (D). *P < 0.05, **P < 0.01, ***P < 0.001.
Figure 4
Figure 4
The prediction and confirmation of a target gene FOXP1 of miR-374b-5p. (A) The complementary sequence of miR-374b-5p in the 3ʹ-UTR of FOXP1. (B) Luciferase activity assay to verify the interaction between miR-374b-5p and FOXP1 (*P < 0.05). (C) Relative mRNA expression of FOXP1 in tissues collected from NSCLC patients (***P < 0.001). (D) Correlation between miR-374b-5p expression and FOXP1 mRNA expression in NSCLC patients.
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