miR-338-3p acts as a tumor suppressor in lung squamous cell carcinoma by targeting FGFR2/FRS2 .

BACKGROUND: Lung cancer refers to the occurrence of malignant tumors in the lung, and squamous cell carcinoma is one of the most common pathological types of non-small cell lung cancer. Studies have shown that microRNAs (miRNAs) play an important role in the occurrence, development, early diagnosis, and treatment of lung cancer. This study aimed to explore the role and possible mechanism of MicroRNA-338-3p (miR-338-3p) in lung squamous cell carcinoma (LUSC).

METHOD: In this study, we compared 238 LUSC patients with relatively high miR-338-3p expression levels with 238 miR-338-3p expression levels in The Cancer Genome Atlas (TCGA)-LUSC dataset using first-line gene set enrichment analysis (GSEA). Second, the mRNA expression of miR-338-3p, FGFR2 , and fibroblast growth factor receptor substrate 2 ( FRS2) in 30 lung cancers and adjacent lung tissues was detected using quantitative real-time polymerase chain reaction (qRT-PCR). Finally, in vitro experiments were conducted, whereby the expression levels of miR-338-3p in lung cancer cells (H1703, SKMES1, H2170, H520) and normal lung epithelial cells (16HBE) were detected using qRT-PCR. miR-338-3p was overexpressed in lung cancer cells (H1703), and the cell proliferation (cell counting kit-8 [CCK8] assay), colony formation, cell apoptosis, cell cycle (BD-FACSVerse assay, Becton Dickinson, Bedford, MA, USA), cell invasion, and migration (Transwell assay, Thermo Fischer Corporation, Waltham, MA, USA) were detected.

RESULTS: We found that the expression of miR-338-3p was significantly reduced in LUSC tissues ( p  ​< ​0.001) and cancer cell lines ( P < 0.01), and miR-338-3p was significantly negatively correlated with the expression of FGFR2 ( P < 0.001) and FRS2 ( P < 0.01). Furthermore, overexpression of miR-338-3p inhibited proliferation ( P < 0.001), migration, and invasion ( P < 0.001) of LUSC cell lines and increased apoptosis in the G1 phase ( P < 0.001) and cell cycle arrest ( P < 0.05).

CONCLUSIONS: Our study demonstrates that miR-338-3p inhibits tumor cell proliferation and migration by targeting FGFR2 and FRS2 in LUSC. We believe that miR-338-3p may be a promising target for the treatment of LUSC.