LINC00514 facilitates cell proliferation, migration, invasion, and epithelial-mesenchymal transition in non-small cell lung cancer by acting on the Wnt/β-catenin signaling pathway

Abstract

The long non-coding RNA (lncRNA) LINC00514 was identified to play an essential oncogenic function in different human cancers, but its effects in non-small cell lung cancer (NSCLC) are yet to be elucidated. In this study, we evaluated the function of LINC00514 in NSCLC. LINC00514 expression and prognosis in NSCLC were analyzed using qRT-PCR and online bioinformatic tools. The bioeffects of LINC0514 in NSCLC cells were examined using cell counting kit-8, colony formation, and transwell assays. Western blotting was used to measure the expression of the target proteins. The LINC00514 regulation of the Wnt/β-catenin signaling pathway was assessed using a specific agonist (LiCl) and luciferase reporter assay. We found that LINC00514 expression was elevated in NSCLC cells and clinical samples and that increased LINC00514 expression predicted poorer patient prognosis. Silencing LINC00514 suppresses proliferation, migration, and invasion of NSCLC cells. Downregulation of LINC00514 inhibited Wnt/β-catenin signaling and epithelial-mesenchymal transition (EMT). Moreover, suppression of the biological phenotypes of NSCLC cells induced by LINC00514 gene silencing was restored after LiCl treatment. Finally, we found that silencing LINC00514 attenuated the growth of xenograft tumors in vivo. Altogether, this study provides the latest convincing evidence that LINC00514 facilitates the malignant biological behavior of NSCLC cells through activation of the Wnt/β-catenin pathway, which might offer a beneficial approach for the treatment of NSCLC.

Crosstalk between lncRNAs and Wnt/β-catenin signaling pathways in lung cancers: From cancer progression to therapeutic response

“…LINC00514 has been shown to be overexpressed in cervical squamous cell carcinoma, gastric cancer, breast cancer and pancreatic cancer [ [77] , [78] , [79] , [80] ]. Zhu et al [ 44 ] indicated that LINC00514 was significantly upregulated in NSCLC and related to poorer prognosis. They observed that silencing LINC00514 decreased the epithelial mesenchymal transition (EMT)-related proteins (E-Cadherin) and Wnt/β-catenin signaling related proteins (β-catenin, cyclinD), while enhancing N-Cadherin expression.…”

“…For instance, LINC00514 increases the migration and invasion of NSCLC. On the one hand, LINC00514 silencing reduced TCF/LEF1 activity, demonstrating yet another way that LINC00514 knockdown inactivated Wnt signaling in NSCLC cells; on the other hand, down-regulation of LINC00514 inhibited migration and invasiveness abilities of cells and tumor xenograft growth [ 44 ]. The Wnt/β-catenin pathway is recognized as carcinogenic.…”

“…TGF, WNTs, and NOTCH are examples of signaling pathways associated with EMT [ 104 ]. The up-regulation of LINC00514 was observed in non-small cell lung cancer lines and clinical samples, which activated Wnt pathway and triggered EMT by positively regulating the expression of Wnt [ 44 ]. Pan et al [ 57 ] found that lncRNA JPX promoted cell proliferation, EMT and cell invasion in lung cancer by inhibiting the tumorigenesis and metastasis processes triggered through miR-33a-5p/Twist1 axis by activating Wnt/β-catenin signaling.…”

The Efficacy and Safety of Anlotinib Plus Etoposide with Cisplatin/Carboplatin in the First-Line Treatment of Lung Cancer: A Phase II Clinical Study

“…Recently, the standard primary therapy for patients with SCLC has been the combination chemotherapy of etoposide and platinum 3 , 17 . Despite the initially high response rate, a significant number of patients experience rapid progression.…”

“…Despite the initially high response rate, a significant number of patients experience rapid progression. More recently, the addition of immune checkpoint inhibitors (such as atezolizumab or bevacizumab) to platinum-etoposide therapy in ES-SCLC patients has shown a transformative effect on OS, leading to a significant paradigm shift in the primary treatment model for SCLC 3 , 17 .…”