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Roles of Wnt/?-Catenin Signaling Pathway Regulatory Long Non-Coding RNAs in the Pathogenesis of Non-Small Cell Lung Cancer.

ABSTRACT: Lung cancer is one of the leading causes of cancer-related mortality worldwide. Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. Long non-coding RNAs (lncRNAs) are promising novel diagnostic and prognostic biomarkers, as well as potential therapeutic targets for lung cancer. Long non-coding RNAs (lncRNAs) have been demonstrated to modulate tumor cells proliferation, cell cycle progression, invasion, and metastasis by regulating gene expression at transcriptional, post-transcriptional, and epigenetic levels. The oncogenic aberrant Wnt/?-catenin signaling is prominent in lung cancer, playing a vital role in tumorigenesis, prognosis, and resistance to therapy. Interestingly, compelling studies have demonstrated that lncRNAs exert either oncogenic or tumor suppressor roles by regulating Wnt/?-catenin signaling. In this review, we aim to present the current accumulated knowledge regarding the roles of Wnt/?-catenin signaling-regulated lncRNAs in the pathogenesis of non-small cell lung cancer (NSCLC). Better understanding of the effects of lncRNAs on Wnt/?-catenin signaling might contribute to the improved understanding of the molecular tumor pathogenesis and to the uncovering of novel therapeutic targets in NSCLC.

SUBMITTER: Lin S

PROVIDER: S-EPMC7280066 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Roles of Wnt/β-Catenin Signaling Pathway Regulatory Long Non-Coding RNAs in the Pathogenesis of Non-Small Cell Lung Cancer.

Lin Shan S Zhen Yu Y Guan Yinghui Y Yi Huanfa H

Cancer management and research 20200603

Lung cancer is one of the leading causes of cancer-related mortality worldwide. Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. Long non-coding RNAs (lncRNAs) are promising novel diagnostic and prognostic biomarkers, as well as potential therapeutic targets for lung cancer. Long non-coding RNAs (lncRNAs) have been demonstrated to modulate tumor cells proliferation, cell cycle progression, invasion, and metastasis by regulating gene expression at transcript ...[more]

PMID: 32581590

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Project description:Beet curly top virus (BCTV) mediated yield loss in sugar beets is a major problem worldwide. The circular single-stranded DNA virus is transmitted by the beet leafhopper. Genetic sources of BCTV resistance in sugar beet are limited and commercial cultivars rely on chemical treatments versus durable genetic resistance. Phenotypic selection and double haploid production have resulted in sugar beet germplasm (KDH13; 13 and KDH4-9; 4) that are highly resistant to BCTV. The molecular mechanism of resistance to the virus is unknown, especially the role of small non-coding RNAs (sncRNAs) during early plant-viral interaction. Using the resistant lines along with a susceptible line (KDH19-17; 19), we demonstrate the role of sugar beet microRNAs (miRNAs) in BCTV resistance during early infection stages when symptoms are not yet visible. The differentially expressed miRNAs altered the expression of their corresponding target genes such as pyruvate dehydrogenase (EL10Ac1g02046), carboxylesterase (EL10Ac1g01087), serine/threonine protein phosphatase (EL10Ac1g01374), and leucine-rich repeats (LRR) receptor-like (EL10Ac7g17778), that were highly expressed in the resistant lines versus susceptible lines. Pathway enrichment analysis of the miRNA target genes showed an enrichment of genes involved in glycolysis/gluconeogenesis, galactose metabolism, starch, and sucrose metabolism to name a few. Carbohydrate analysis revealed altered glucose, galactose, fructose, and sucrose concentrations in the infected leaves of resistant versus susceptible lines. We also demonstrate differential regulation of BCTV derived sncRNAs in the resistant versus susceptible lines that target sugar beet genes such as LRR (EL10Ac1g01206), 7-deoxyloganetic acid glucosyltransferase (EL10Ac5g12605), and transmembrane emp24 domain containing (EL10Ac6g14074) and altered their expression. In response to viral infection, we found that plant derived miRNAs targeted BCTV capsid protein/replication related genes and showed differences in expression among resistant and susceptible lines. The data presented here demonstrate the contribution of miRNA mediated regulation of metabolic pathways and cross-kingdom RNA interference (RNAi) in sugar beet BCTV resistance.

Project description:BackgroundWnt2 is overexpressed and able to promote tumorigenesis in many types of cancer. However, its expression and role in lung cancer has not been well clarified yet. In this study, we aims to investigate the expression pattern, clinical significance and the underlying molecular mechanism of Wnt2 in non-small lung cancer (NSCLC).MethodsImmunohistochemical staining and ELISA assays were applied to detect Wnt2 level in tumor tissue and serum. EDU incorporation assays and colony formation assays were used to evaluate the growth-promoting effect of Wnt2 in vitro. Then we performed western blot and immunofluorescence assays to detect the activation of WNT signaling pathway. Finally mice engrafted with NSCLC tumor cells were used to assess the role of Wnt2 in vivo.ResultsImmunohistochemical staining consisting of 264 NSCLC tumor tissues showed that a high level of Wnt2 was associated with a poor overall survival (OS) and relapse-free survival (RFS) of NSCLC patients (P = 0.002 and 0.0005, respectively). Multivariate analysis presented that Wnt2 level in tumor tissue was an independent prognostic factor (P = 0.049 for OS and P = 0.002 for RFS, respectively). Furthermore, ELISA assays for 181 individuals (116 NSCLC and 65 controls) revealed that serum Wnt2 levels in adenocarcinoma was significantly higher than that in healthy volunteers (P < 0.0001). In vitro H460 cell line stably overexpressing Wnt2 showed enhanced growth activity than the control cells whereas knockdown of Wnt2 by siRNA in H1299 cells resulted in decreased growth activity. Additionally, Wnt2 level in tumor tissues was significantly associated with Ki-67 level (rs: 0.316; P < 0.0001). Immunofluorescence and Western blot assays detected the translocation of β-catenin from cytoplasm into nucleus, which indicated that Wnt2 probably promotes proliferation by activating WNT/β-catenin pathway. In vivo H460 cells expressing exogenous Wnt2 showed increased growth-promoting effect in Balb/c nude mice than control cells.ConclusionsThe present study for the first time suggested that Wnt2 was both a prognostic and a diagnostic biomarker for NSCLC. Tumor-derived Wnt2 can promote growth activity of NSCLC cells through activating WNT/β-catenin signaling pathway.

Dataset Information

Roles of Wnt/?-Catenin Signaling Pathway Regulatory Long Non-Coding RNAs in the Pathogenesis of Non-Small Cell Lung Cancer.

Publications

Roles of Wnt/β-Catenin Signaling Pathway Regulatory Long Non-Coding RNAs in the Pathogenesis of Non-Small Cell Lung Cancer.

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