LINC00943 regulates miR-1252-5p/YWHAH axis to promote tumor proliferation and metastasis in lung adenocarcinoma

Abstract

Lung cancer is the most common malignant tumor worldwide. In recent years, the incidence of lung adenocarcinoma (LAD) has increased significantly, with an unfavorable 5-year survival rate. Long non-coding RNAs (lncRNAs) have been shown to play a significant role in the emergence, growth, and metastasis of tumors. However, the functional role and mechanism of LINC00943 in LAD progression have not yet been investigated. Aberrant expressions of LINC00943, miR-1252-5p, and YWHAH were determined by RT-qPCR and Western blot analyses. The binding relationship between miR-1252-5p and LINC00943 or YWHAH was examined by Pearson's correlation analysis, RNA pull-down, and dual-luciferase reporter assays. MTT assay was conducted to measure cell viability and colony formation assay was performed to evaluate cell proliferation potential. Transwell assay was used to investigate cell migration and invasion and flow cytometry was applied to evaluate cell apoptosis. We found that LINC00943 was highly expressed in LAD tissue samples and cell lines and was a reliable biomarker with high sensitivity, and specificity (P < 0.0001; AUC: 0.8966) for LAD detection. LINC00943 was mainly localized in the cytoplasm. In vitro, LINC00943 promoted LAD cell proliferation, migration, and invasion; however, silencing LINC00943 inhibited LAD tumor metastasis. Mechanistically, LINC00943 was competitively bound with miR-1252-5p to enhance YWHAH expression. Moreover, LINC00943 silencing sponged miR-1252-5p to inhibit YWHAH, thereby retraining LAD cell malignant behaviors. In summary, LINC00943 facilitates LAD cell malignancy through sponging miR-1252-5p to upregulate YWHAH. LINC00943 is a novel lncRNA that serves as an oncogene and might be used as a prognostic biomarker for LAD.