LncRNA T376626 is a promising serum biomarker and promotes proliferation, migration, and invasion via binding to LAMC2 in triple-negative breast cancer
Rongqiao He, Bin Xiao, Ting Lei, Junfeng Xuan, Yi Zhu, Zhenzhan Kuang, Jiahui Liu, Jia He, Linhai Li, Zhaohui Sun
Abstract
PURPOSE: Circulating long noncoding RNAs (lncRNAs) have been reported to serve as biomarkers for cancer diagnosis. Here, we identified the clinical diagnostic value and biological function of lncRNA T376626 in triple-negative breast cancer (TNBC). METHOD: A genome-wide lncRNA microarray was used to screen promising serum-based lncRNA biomarkers. The expression of candidate serum lncRNAs was validated in 282 breast cancer (BC) patients and 78 healthy subjects. The diagnostic value of serum lncRNA T376626 was determined by receiver operating characteristic (ROC) curve. RNA fluorescent in situ hybridization (FISH) and RNAScope ISH assays were conducted to examine the expression and localization of lncRNA T376626 in TNBC cells and BC tissues. Kaplan-Meier analysis was conducted to evaluate the relationship between lncRNA T376626 and BC patients' overall survival (OS) rate. CCK-8, colony-forming, wound healing and Transwell assays were performed to investigate the biological function of lncRNA T376626 on cell proliferation, migration, and invasion in two TNBC cell lines. Cell apoptosis-, cell cycle- and epithelial-mesenchymal transition (EMT)-related biomarkers were quantified by western blots. The lncRNA T376626 binding proteins were screened and identified by RNA pulldown. RESULTS: LncRNA T376626 level was significantly higher in TNBC serums and tissues. Higher levels of lncRNA T376626 were positively associated with a higher pathological differentiation stage, more aggressive molecular subtype, and poor prognosis in BC and TNBC patients. The area under the curve (AUC) of serum lncRNA T376626 was 0.842. Overexpression (Knockdown) of lncRNA T376626 significantly promoted (inhibited) TNBC cell proliferation, migration, and invasion, possibly by regulating several cell cycle, cell apoptosis and EMT biomarkers. LAMC2 were identified as lncRNA T376626-binding proteins. LAMC2 facilitated TNBC proliferation and metastasis through lncRNA T376626. CONCLUSIONS: LncRNA T376626 may serve as a TNBC serum-based diagnostic and prognostic biomarker and play an oncogenic role in TNBC progression through binding to LAMC2.