LncRNA CRNDE is activated by SP1 and promotes osteosarcoma proliferation, invasion, and epithelial‐mesenchymal transition via Wnt/β‐catenin signaling pathway

Abstract

Long noncoding RNAs (lncRNAs) were identified as a vital part in the development and progression of cancer in recent years. Colorectal neoplasia differentially expressed (CRNDE), a lncRNA, functions as an oncogene in some malignant neoplasias, but its role in the progression of osteosarcoma (OS) is still poorly understood. To dissect the difference in the expression of CRNDE, quantitative real-time polymerase chain reaction was utilized to evaluate it in OS tissues and cell lines (U2OS, MG63, and MNNG/HOS) compared with that in the adjacent normal tissues/osteoblast cells (hFOB1.19). The role of CRNDE in OS lines was assessed using Cell Counting Kit-8, colony formation, 5-ethynyl-2′-deoxyuridine staining, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling staining, flow cytometry, Transwell assays, and Western blot, respectively. The results demonstrated that the expression of CRNDE was high in OS tissues and cell lines, and partly induced by SP1. CRNDE knockdown attenuated OS cell proliferation and invasion and induced apoptosis and G0/G1 arrest. Moreover, the expression of mesenchymal markers N-cadherin, Vimentin and Snail were downregulated, while the expression of epithelial markers E-cadherin and ZO-1 were conversely upregulated due to CRNDE knockdown. The mechanistic investigations showed that CRNDE promoted glycogen synthase kinase-3β phosphorylation to activate the Wnt/β-catenin pathway. The results suggested that lncRNA CRNDE indeed contributed to OS proliferation, invasion, and epithelialmesenchymal transition, working as an oncogene, demonstrating that lncRNA CRNDE may be a valid therapeutic target for the OS.

LINC01123 enhances osteosarcoma cell growth by activating the Hedgehog pathway via the miR‐516b‐5p/Gli1 axis

“…25 In triple negative breast cancer, LINC01123, activated by FOXC1, regulates cell growth through miR-663a/CMIP signaling. 6 In this study, we observed that the expression of LINC01123 was clearly upregulated in OS cell lines. Moreover, LINC01123 promoted cell proliferation, metastasis, and stemness in vitro.…”

“…8 Accumulating evidence indicates that LINC01123 promotes tumor growth in various cancers. 6,9 However, the function of LINC01123 in OS remains unknown.…”

Profiling pro-neural to mesenchymal transition identifies a lncRNA signature in glioma

“…As expected, a strong relationship between several of these lncRNAs and mesenchymal transition in solid tumors had been reported in the literature. For example, mesenchymal transition was reinforced by CRNDE via the Wnt/β-catenin pathway in osteosarcoma [ 18 ], and lncRNA PVT1 sponged miR-195 to enhance EMT and induce therapeutic resistance in cervical cancer [ 19 ]. Therefore, we identified 149 lncRNAs that might play important roles in regulating mesenchymal transition.…”

LncRNA CRNDE Promotes ATG4B-Mediated Autophagy and Alleviates the Sensitivity of Sorafenib in Hepatocellular Carcinoma Cells

“…Nevertheless, it remains unknown how sorafenib elevates CRNDE level. Previous reports have shown that some factors such as RNA binding proteins, transcription factors, epigenetic modification, miRNAs, or specific signal pathways participate in the regulation of CRNDE ( Wang et al, 2015 ; Huan et al, 2017 ; Jiang et al, 2017 ; Kiang et al, 2017 ; Ding et al, 2020 ). Sorafinib may upregulate CRNDE through one or several above factors, or other mechanism(s).…”