Long non-coding RNA (lncRNA) is a class of endogenous RNA with a length of more than 200 nucleotides, which is emerging as a pivotal player in cancer development and progression. However, the functional roles of many members in this class remain largely uncharacterized. In the present study, we explored the biological relevance of linc02042 in esophageal squamous cell carcinoma (ESCC). qRT-PCR was used to detect the levels of linc02042 and c-Myc. Western blot was used to assess protein expression level. CCK-8 and Transwell assays were employed to test ESCC cell proliferation and invasion, respectively. The mice study including xenograft tumor and lung metastasis models was used to determine the role of linc02042 in vivo. RNA pull-down, ChIP and luciferase reporter assays were employed to test the relationship between linc02042, YBX1 and c-Myc. Linc02042 was found to be markedly upregulated in ESCC cell lines, tissues and plasma, and was closely correlated with malignant clinical features. Knockdown of linc02042 significantly inhibited ESCC cell viability and invasion in vitro as well as tumor growth and lung metastasis in vivo, whereas overexpression of linc02042 resulted in the opposite results. Mechanistically, linc02042 acted as a scaffold for YBX-1 binding to the 3′-UTR of c-Myc mRNA, leading to enhanced c-Myc mRNA stability, thereby facilitating ESCC growth and metastasis. Moreover, in turn, c-Myc was able to transcriptionally elevate linc02042 by directly binding to the E-box motif proximal to the transcription start site (TSS) of linc02042 promoter. Clinically, linc02042 was identified as an effective diagnostic and prognostic biomarker for ESCC patients, and its expression was strongly positively correlated with c-Myc expression in ESCC tissues. Our data suggest that linc02042 plays an important tumor-promoting role in ESCC, which lays a foundation for considering it as a potential target for ESCC patients.

中文翻译：

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YBX1介导的linc02042和c-Myc的新型正反馈环促进食管鳞状细胞癌的肿瘤发生和转移


长非编码RNA（lncRNA）是一类长度超过200个核苷酸的内源性RNA，正在成为癌症发生和进展的关键参与者。然而，该类别中许多成员的功能角色在很大程度上仍然不明确。在本研究中，我们探讨了 linc02042 在食管鳞状细胞癌 (ESCC) 中的生物学相关性。采用qRT-PCR检测linc02042和c-Myc的水平。 Western blot用于评估蛋白质表达水平。 CCK-8和Transwell实验分别用于测试ESCC细胞的增殖和侵袭。包括异种移植肿瘤和肺转移模型在内的小鼠研究用于确定 linc02042 在体内的作用。采用 RNA Pull-down、ChIP 和荧光素酶报告基因测定来测试 linc02042、YBX1 和 c-Myc 之间的关系。 Linc02042被发现在ESCC细胞系、组织和血浆中显着上调，并且与恶性临床特征密切相关。 linc02042的敲低在体外显着抑制ESCC细胞的活力和侵袭，在体内显着抑制肿瘤生长和肺转移，而linc02042的过表达导致相反的结果。从机制上讲，linc02042充当YBX-1与c-Myc mRNA 3'-UTR结合的支架，导致c-Myc mRNA稳定性增强，从而促进ESCC生长和转移。此外，反过来，c-Myc 能够通过直接结合靠近 linc02042 启动子转录起始位点 (TSS) 的 E-box 基序来转录升高 linc02042。临床上，linc02042被确定为ESCC患者的有效诊断和预后生物标志物，其表达与ESCC组织中c-Myc表达呈强正相关。 我们的数据表明linc02042在ESCC中发挥重要的促肿瘤作用，这为将其作为ESCC患者的潜在靶点奠定了基础。