p53-Induced LINC00893 Regulates RBFOX2 Stability to Suppress Gastric Cancer Progression

Abstract

Long noncoding RNAs (lncRNAs) have been reported to regulate diverse tumorigenic processes. However, little is known about long intergenic non-protein coding RNA 00893 (LINC00893) and its role in gastric cancer (GC). Herein we investigated its biological functions and molecular mechanism in GC. LINC00893 was decreased in GC tissues but significantly elevated in AGS cells after treatment with Nutlin-3. In GC patients, it was found that low expression of LINC00893 was correlated with tumor growth, metastasis and poor survival. Functionally, overexpression of LINC00893 suppressed the proliferation, migration and invasion of GC cells. Mechanistically, LINC00893 regulated the expression of epithelial-mesenchymal transition (EMT)-related proteins by binding to RNA binding fox-1 homolog 2 (RBFOX2) and promoting its ubiquitin-mediated degradation, thus suppressing the EMT and related functions of GC. In addition, the transcription factor p53 can regulate the expression of LINC00893 in an indirect way. Taken together, these results suggested that LINC00893 regulated by p53 repressed GC proliferation, migration and invasion by functioning as a binding site for RBFOX2 to regulate its stability and the expression of EMT-related proteins. LINC00893 acts as a tumor-inhibiting lncRNA that is induced by p53 in GC and regulates EMT by binding to RBFOX2, thus providing a novel experimental basis for the clinical treatment of GC.

Integrated pan-cancer analysis reveals the immunological and prognostic potential of RBFOX2 in human tumors

“…RBFOX2, a well-characterized regulator of alternative splicing, has been reported involved in EMT and contributes to metastasis of several cancers (Yeo et al, 2009;Braeutigam et al, 2014). RBFOX2 was overexpression and promoted the migration of gastric cancer cells (Ou et al, 2021), which was consistent with what we have found that RBFOX2 was high in STAD tissues than normal tissues. The mRNA level of RBFOX2 was significantly upregulated in nasopharyngeal carcinoma (NPC) tissues, correlating with the initiation of NPC cell tumorigenesis (Luo et al, 2021).…”

Placental circadian lincRNAs and spontaneous preterm birth

“…Both LINC00893 and LINC00265 have been linked to circadian rhythm pathways in cancers (Ge et al, 2019;Li et al, 2021). The five lincRNAs identified here have also been reported to be involved in proliferation, migration, invasion, apoptosis, inflammation, angiogenesis, and epithelial-mesenchymal transition in various cancer cells (Li et al, 2020;Zhang et al, 2020;Wang et al, 2021a;Wang et al, 2021b;Ou et al, 2021;Zhi et al, 2021). These cancer pathways partially overlap with our findings from the pathway analysis of these five circadian lincRNAs (see below for details).…”

LncRNA and mRNA profiles of human milk-derived exosomes and their possible roles in protecting against necrotizing enterocolitis

“…37 LINC00893 (ENSG00000241769) has been reported to serve as a novel biomarker and therapeutic target of various cancers such as gastric cancer, thyroid cancer and colon cancer. 38–40 Furthermore, overexpression of MIR497HG (ENSG00000267532) could influence the progression of diabetic retinopathy by suppressing the proliferation and migration of human retinal endothelial cells. 41 More importantly, LINC00263 (ENSG00000235823) and LINC00702 (ENSG00000233117) have been respectively demonstrated to be associated with the activity of the NF-κB-signaling pathway and Wnt/β-catenin signaling.…”