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Objective: To investigate the biological function and clinicopathological significance of the TGFβ-induced long non-coding RNA (lncRNA) TBULC in non-small cell lung cancer (NSCLC) and to analyze its potential value in clinical diagnosis and treatment. Methods: RT-qPCR was used to detect the expression level of TBULC in NSCLC cells and tissues, and the correlation between the TBULC expression level and clinicopathological characteristics was analyzed. A cytoplasmic/nuclear fractionation assay was performed to define the cellular localization of the TBULC. A rapid amplification of cDNA ends (RACE) assay was performed to acquire the full-length sequence of the TBULC. Stable TBULC overexpression and TBULC knockdown cell clones were constructed by lentiviral infection, and Transwell assays were used to explore the effect of the TBULC on cell invasion and migration. Results: Stimulation with TGFβ in NSCLC cell lines significantly upregulated the expression level of the nuclear-localized lncRNA TBULC. The RACE assay indicated that the full-length TBULC sequence was 1,020 nucleotides, and the sequence was located on chromosome 15. Cell function experiments showed that the TBULC played a crucial role in promoting NSCLC metastasis. Knockdown of TBULC significantly suppressed the invasion and migration of NSCLC cells, and overexpression of TBULC had the opposite effects. The expression level of TBULC in 106 NSCLC tumor tissues was significantly higher than that in adjacent normal tissues, and TBULC was proven to be an independent prognostic factor in NSCLC patients [ p = 0.030, OR = 0.513 (0.281–0.936)]. Conclusion: The TGFβ-induced lncRNA TBULC was upregulated in NSCLC and promoted the invasion and migration of NSCLC cells. TBULC was an independent prognostic factor and might be a potential biomarker for predicting the prognosis of NSCLC patients. [ABSTRACT FROM AUTHOR]

Abstract: The long non‐coding RNA GAS5 has been reported as a tumor suppressor in many cancers. However, its functions and mechanisms remain largely unknown in esophageal squamous cell carcinoma (ESCC). In this study, we found that GAS5 was over‐expressed in ESCC tissue compared with that in normal esophageal tissue in a public database. Functional studies showed that GAS5 could inhibit ESCC cell proliferation, migration and invasion in vitro. Further analysis revealed that GAS5 was regulated by interferon (IFN) responses via the JAK‐STAT pathway. Moreover, as an IFN‐stimulated gene (ISG), GAS5 was a positive regulator of IFN responses. The feedback loop between GAS5 and the IFN signaling pathway plays an important antitumor role in ESCC, thus providing novel potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Abstract: The transforming growth factor β (TGF-β) signaling pathway plays anti- and pro-tumoral roles in the vast majority of cancers, and long noncoding RNAs have been reported to play key roles in the highly contextual response process. However, the roles of long noncoding RNAs (lncRNAs) in TGF-β signaling in esophageal squamous cell carcinoma (ESCC) remain unknown. In this study, we performed RNA-seq to compare lncRNAs expression levels between TGF-β1-treated and untreated ESCC cells and observed that NF-kappaB-interacting lncRNA (NKILA) was remarkably upregulated by the classical TGF-β signaling pathway. RNA profiling of 39 pairs ESCC tumor and adjacent nontumor samples using RT-qPCR demonstrated that NKILA is significantly downregulated in ESCC tumor tissues, and NKILA expression levels were significantly decreased in advanced tumor tissues (III and IV) compared to early stages (I and II) (p < 0.01). Gain- and loss-of-function assays showed that NKILA inhibited ESCC cell metastasis in vitro and in vivo, and mechanism studies showed that NKILA repressed MMP14 expression by inhibiting IκBα phosphorylation and NF-κB activation. Collectively, these findings suggest that the TGF-β-induced lncRNA NKILA has potential as an antimetastasis therapy.Key messages: Long noncoding RNA NKILA could be remarkably upregulated by classical TGF-β signal pathway in ESCC.NKILA was significantly downregulated in esophageal squamous cell carcinoma and negatively correlated with TNM stage.NKILA inhibits ESCC cell metastasis via repressing MMP14 expression by suppressing the phosphorylation of IκBα and NF-κB activation. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) play critical roles in multiple cellular processes in non-small cell lung cancer (NSCLC); however, the involvement of lncRNAs in the transforming growth factor-beta (TGFβ) signaling pathway, the critical tumor cell epithelial-mesenchymal transition (EMT) and metastasis pathway, remains poorly understood. To address this issue, we compared the lncRNAs expression patterns of NSCLC cells treated with and without TGFβ1 treatment. We observed that one of the most prominent hits, TGFβ-induced lncRNA (TBILA), promoted NSCLC progression and was upregulated in tumor tissues. Upregulated TBILA promotes human germinal center-associated lymphoma (HGAL) expression by binding to the Smad transcription factor complex, thereby enhancing RhoA activation. In addition, TBILA induces the S100A7-c-Jun activation domain-binding protein 1 (JAB1) pathway by binding to nuclear S100A7 and enhances pro-survival pathways in NSCLC. These findings have provided us with a new perspective regarding the regulation of the TGFβ signaling pathway in NSCLC and suggest that the lncRNA TBILA can serve as a target for anticancer therapies. [ABSTRACT FROM AUTHOR]