Clinical Significance of miR-183-3p and miR-182-5p in NSCLC and Their Correlation

Abstract

Purpose: Accumulating evidence has indicated that dysregulated microRNAs (miRNAs) are involved in cancer progression. In this study, we evaluated the clinicopathologic significance of miR-183-3p and miR-182-5p, and the role of miR-183-3p in non-small-cell lung cancer (NSCLC) progression.

Patients and methods: Seventy-six NSCLC patients from Beijing Chest Hospital were included. The expression of miR-183-3p and miR-182-5p was evaluated by real-time quantitative polymerase chain reaction (RT-qPCR). Then, cell growth curve assays and colony formation assays were performed. Bioinformatics analysis of TCGA database was performed to explore the clinicopathological significance and prognostic value.

Results: miR-183-3p and miR-182-5p were significantly increased in NSCLC tumor tissues (both P < 0.0001) and were positively correlated (r = 0.8519, P < 0.0001). miR-183-3p (P = 0.0444) and miR-182-5p (P = 0.0132) were correlated with tumor size. In addition, miR-183-3p (P = 0.0135) and miR-182-5p (P = 0.0009) were upregulated in normal lung tissues from smokers. In vitro, miR-183-3p was correlated with cell proliferation. In addition, bioinformatics analysis indicated that miR-183-3p was correlated with poor prognosis (P = 0.0466) and tumor size (P = 0.0017). In addition, miR-183-3p was higher in lung squamous carcinoma (LUSC) tissue (P < 0.0001) than in lung adenocarcinoma (LUAD) tissue, and miR-183-3p was higher in the tumor tissue of smokers (P = 0.0053) than in that of nonsmokers.

Conclusion: Upregulation of miR-183-3p and miR-182-5p may play an oncogenic role in NSCLC. miR-183-3p could be used as a potential prognostic biomarker and therapeutic target to manage lung cancer.

Keywords: NSCLC; miR-182-5p; miR-183-3p; non-small-cell lung cancer; prognosis; proliferation.

Figure 1

Relative miR-183-3p or miR-182-5p expression in cancer and normal tissues detected by RT-qPCR. (A and B) Relative miR-183-3p and miR-182-5p expression in cancer and normal tissues of the included patients. **Statistical significance P < 0.01. (C and D) Relative miR-183-3p and miR-182-5p expression in the NSCLC TNM stage I, stage II and stage III+IV groups. (E and F) Relative miR-183-3p and miR-182-5p expression in cancer and normal tissues of different histologic types. (G and H) Figure 1G. Relative miR-183-3p and miR-182-5p expression in cancer and normal tissues of nonsmokers and smokers. *Statistical significance P < 0.05. **Statistical significance P < 0.01.

Figure 2

Relative miR-183-3p or miR-182-5p expression in NSCLC cell lines and BEAS-2B cells detected by RT-qPCR. (A) Relative miR-183-3p expression in various NSCLC cell lines and BEAS-2B cell lines. *Statistical significance P < 0.05. **Statistical significance P < 0.01. (B) Relative miR-182-5p expression in various NSCLC cell lines and BEAS-2B cell lines. **Statistical significance P < 0.01.

Figure 3

Correlation between the relative expression of miR-183-3p and miR-182-5p detected by RT-qPCR. (A) Correlation between relative miR-183-3p expression and relative miR-182-5p expression. (B) Relative miR-182-5p expression in a miR-183-3p overexpression or suppression cell model. H23 or H226 control, H23 or H226 cell lines transfected with RNA-TransMate only. H23 si-miR-183-3p, H23 cell line transfected with the miR-183-3p inhibitor. H226 miR-183-3p OE, H226 cell line transfected with the miR-183-3p mimic. *Statistical significance P < 0.05. **Statistical significance P < 0.01.

Figure 4

Proliferation ability changes in the miR-183-3p overexpression or suppression cell models. (A–C) CCK-8 assays were performed to measure the proliferation abilities of A549, H226 and BEAS-2B cells transfected with the miR-183-3p mimic. miR-183-3p OE, cells transfected with the miR-183-3p mimic. (D) CCK-8 assays were performed to measure the proliferation ability of H1395 cells transfected with the miR-183-3p inhibitor. si-miR-183-3p, cells transfected with the miR-183-3p inhibitor. (E–G) Colony formation assays were conducted to measure the proliferation abilities of A549, H226 and BEAS-2B cells transfected with the miR-183-3p mimic. Significant differences could be observed from representative pictures of culture plates (E), number of colonies (F) and colony formation rate (G). miR-183-3p OE, cells transfected with the miR-183-3p mimic. *Statistical significance P < 0.05. **Statistical significance P < 0.01. (H–J) Colony formation assays were conducted to measure the proliferation ability of H1395 cells transfected with the miR-183-3p mimic. Significant differences could be observed from representative pictures of culture plates (H), number of colonies (I) and colony formation rate (J). si-miR-183-3p, cells transfected with the miR-183-3p inhibitor. *Statistical significance P < 0.05.

Figure 5

Bioinformatics analysis of the clinicopathological significance and prognostic value of miR-183-3p in TCGA database. (A–C) Relative miR-183-3p expression among different tumor sizes (A), histological types (B) and smoking histories (C). **Statistical significance P < 0.01. (D–F) Kaplan-Meier curves of NSCLC cases in TCGA database stratified by miR-183-3p expression (bottom 10% [n = 96] versus top 10% [n = 96]) (D). Further respective analysis in LUAD cases (E) and LUSC cases (F) showed different prognostic value.