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Background: Opa-interacting protein 5 antisense transcript 1 (OIP5-AS1) has been demonstrated to play vital roles in development and progression of tumors such as gastric cancer (GC). However, the detailed molecular mechanism of OIP5-AS1 has not been completely elucidated. Our study aimed to investigate the role and the epigenetic regulation mechanism of OIP5-AS1 in GC. Methods: OIP5-AS1 expression in GC tissues was detected by RT-qPCR. Loss- and gain-of-function experiments were conducted to assess the biological function of OIP5-AS1 in vitro and in vivo. The interaction of OIP5-AS1 with insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) or heterogeneous nuclear nucleoprotein A1 (hnRNPA1) was verified by bioinformatics analysis, RNA pull-down assays, and RNA immunoprecipitation assays. Results: In this study, we identified that OIP5-AS1 is specifically overexpressed in GC tumor tissues and cell lines and correlated with a poor prognosis. The loss of OIP5-AS1 suppressed the proliferation, migration, invasion, epithelial–mesenchymal transition (EMT), and glycolysis of GC cells, but the ectopic expression of OIP5-AS1 had the opposite impact. Meanwhile, knockdown of OIP5-AS1 inhibited tumor growth in patient-derived xenograft models, as well as repressed tumor metastasis. Mechanistically, IGF2BP3 could bind to OIP5-AS1 by N6-methyladenosine (m6A) modification sites on OIP5-AS1, thereby stabilizing OIP5-AS1. Moreover, OIP5-AS1 prevented Trim21-mediated ubiquitination and degradation of hnRNPA1, stabilizing hnRNPA1 protein and promoting the malignant progression of GC by regulating PKM2 signaling pathway. Conclusions: In conclusion, this study highlighted that OIP5-AS1 is an oncogenic m6A-modified long non-coding RNA (lncRNA) in GC and that IGF2BP3/OIP5-AS1/hnRNPA1 axis may provide a potential diagnostic or prognostic target for GC. [ABSTRACT FROM AUTHOR]

Emerging evidence has uncovered that noncoding RNAs (ncRNAs) contribute to the development of hepatocellular carcinoma (HCC). Nevertheless, the functions of the majority of long ncRNAs (lncRNAs) in HCC are unknown. Here, we intend to probe the function of lncRNA NUTM2A-AS1 in the evolvement of HCC and the related mechanism. Expression levels of lncRNA NUTM2A-AS1, miR-186-5p and KLF7 mRNA in HCC tissues and adjacent non-tumor tissues were monitored. Gain- or loss-of-function assays were utilized to investigate the biological functions of lncRNA NUTM2A-AS1, miR-186-5p and KLF7 in HCC cell lines (including HCCLM3 and Huh7). Western blot was implemented for the detection of the epithelial–mesenchymal transition (EMT)-related proteins (including E-cadherin, Vimentin and Snail), KLF7, Wnt, β-catenin, and stemness-related proteins (Nanog, OCT4, YKL40, and CD133). Furthermore, the targeted associations between lncRNA NUTM2A-AS1, miR-186-5p, and KLF7 were verified by bioinformatics analysis, dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. As a result, lncRNA NUTM2A-AS1 and KLF7 profiles were heightened in the HCC tissues versus adjacent normal tissues, while miR-186-5p had the opposite expression tendency. Up-regulation of lncRNA NUTM2A-AS1 was related to tumor size, advanced tumor stage, and lymph node metastasis of HCC patients. Functionally, overexpression of lncRNA NUTM2A-AS1 heightened HCC cells' growth, invasion, EMT, and stemness and repressed their apoptosis by activating the Wnt/β-catenin pathway. In contrast, up-regulation of miR-186-5p or inhibition of KLF7 had reverse effects. In vivo, lncRNA NUTM2A-AS1 overexpression facilitated tumor growth and EMT, accompanied by declined miR-186-5p levels and enhanced KLF7 expression. The mechanistic studies revealed that miR-186-5p served as a common target of lncRNA NUTM2A-AS1 and KLF7. As hinted by the rescue experiments, NUTM2A-AS1 partly abated miR-186-5p-mediated anti-tumor effects in HCC cells, whereas KLF7 knockdown reversed the promotive effects of NUTM2A-AS1. LncRNA NUTM2A-AS1 accelerated the evolution of HCC by up-regulating the KLF7/Wnt/beta-catenin pathway through sponging miR-186-5p. [ABSTRACT FROM AUTHOR]

Purpose: Bromodomain PHD-finger transcription factor (BPTF) is a chromatin-mediated regulation of transcription factor, playing an important role in embryogenesis and differentiation. Epithelial-mesenchymal transition (EMT) has a pivotal role in colorectal cancer (CRC) progression, sharing the similar characteristic with BPTF. Therefore, the aim of this study was to examine the expression and clinical value of BPTF and the correlation with EMT markers in patients with CRC. Methods: Real-time PCR and Western blot were performed to evaluate the mRNA and protein expression levels of BPTF in 20 pairs of fresh-frozen CRC and non-tumor adjacent tissues (NATs). The expressions of BPTF, vimentin and E-cadherin were examined by immunohistochemical staining in 105 cases of paraffin-embedded primary CRC specimens. In addition, the clinicopathological significance and the prognostic value of BPTF, vimentin and E-cadherin expression were further determined. Then, the correlation of BPTF with vimentin and E-cadherin was also explored. Results: BPTF mRNA and protein expression were significantly overexpressed in CRC tissues when compared with paired NATs ( P < 0.01). The expression levels of BPTF and vimentin in CRC paraffin-embedded specimens were significantly higher than the expression in NATs ( P < 0.01), while the expressions of E-cadherin in tumors were obviously lower than in NATs ( P < 0.01). Tumors with high expression of BPTF and vimentin, as well as low expression of E-cadherin, were significantly correlated with various adverse clinicopathological factors ( P < 0.05). The CRC patients with a high BPTF or vimentin expression had shorter overall survival than those with lower expression ( P < 0.05). Furthermore, univariate analysis and multivariate analysis showed that high BPTF expression was an independent prognostic factor for patients with CRC. The last and more interesting Spearman rank correlation analysis and microscopic observation found that the expression of BPTF obviously correlated with the expression of EMT markers vimentin and E-cadherin. Conclusion: Our results strongly suggested that the high BPTF expression was significantly correlated with tumor progression and may be a potent prognostic marker of CRC. Moreover, BPTF expression was significantly associated with EMT markers vimentin and E-cadherin. [ABSTRACT FROM AUTHOR]

Background/Aims: Epithelial-mesenchymal transition (EMT) plays an important role in hepatocellular carcinoma (HCC) dissemination. Bromodomain PHD-finger transcription factor (BPTF) could regulate embrogenesis and stem cell differentiation, and it may be involved in tumor progression and EMT. In this study, we aimed to determine BPTF, E-cadherin and vimentin expression in tumor tissues and the clinical significance in relation to HCC. Methods: The BPTF, vimentin and E-cadherin expression of 106 HCC tissue samples was examined by immunohistochemical staining. Results: BPTF and vimentin showed high expression and E-cadherin showed low expression in HCC. BPTF is associated with the tumor number, vascular invasion, Edmondson-Steiner grade, TNM stage and recurrence ( P < 0.05). Vimentin is positively correlated with tumor size, tumor number, vascular invasion, Edmondson-Steiner grade, TNM stage and recurrence ( P < 0.05). E-cadherin is negatively correlated with tumor number, Edmondson-Steiner grade, TNM stage and recurrence ( P < 0.05). Survival analysis has shown that high expression of BPTF and vimentin indicates poorer overall and disease-free survival ( P < 0.05). Multivariate analysis shows that BPTF is an independent marker for survival prediction ( P = 0.015). Additionally, high BPTF expression is correlated with high vimentin expression and low E-cadherin expression ( P < 0.05). Conclusion: High BPTF expression may be an independent marker for survival prediction in HCC patients and is probably involved in EMT. [ABSTRACT FROM AUTHOR]