Translational Medical Center, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, 450007, PR China.
Department of Medicine, University of California, San Francisco, USA.
Cancer Lett. 2020 Nov 28;493:217-227. doi: 10.1016/j.canlet.2020.09.001. Epub 2020 Sep 6.
The expression of lncRNA ESCCAL-1 is upregulated in esophageal squamous cell carcinoma (ESCC). However, the molecular pathways regulated by ESCCAL-1 in esophageal cancer remain obscure. We found that high expression of the lncRNA ESCCAL-1 in human ESCC tumors correlated with worse clinicopathologic features. Furthermore, depletion of ESCCAL-1 in ESCC models inhibited the cellular processes associated with malignancy, including proliferation, migration and invasion, resistance to apoptosis, and impaired tumor growth in mice. Using a combinatorial approach, we discovered that ESCCAL-1 regulates malignant phenotypes in ESCC by acting as a molecular sponge for miR-590-3p. This interaction prevents miR-590-3p from suppressing APOBEC3G expression. Increased APOBEC3G was also a biomarker of worse clinicopathologic features in human ESCC tumors. Depletion of ESSCAL-1 or APOBEC3G, or overexpression of miR-590-3p resulted in increased apoptosis due to downregulation of the PI3K/Akt signaling. This study demonstrates that the lncRNA ESCCAL-1 promotes malignant features of ESCC by relieving the inhibitory effect of miR-590-3p on APOBEC3G expression and identifies potential biomarkers or therapeutic targets to improve ESCC treatment outcomes.
长链非编码 RNA ESCCAL-1 在食管鳞状细胞癌（ESCC）中表达上调。然而，ESCCAL-1 调节食管癌的分子途径仍不清楚。我们发现，长链非编码 RNA ESCCAL-1 在人 ESCC 肿瘤中的高表达与更差的临床病理特征相关。此外，在 ESCC 模型中敲低 ESCCAL-1 抑制了与恶性相关的细胞过程，包括增殖、迁移和侵袭、抗凋亡以及在小鼠中肿瘤生长受损。通过组合方法，我们发现 ESCCAL-1 通过作为 miR-590-3p 的分子海绵来调节 ESCC 的恶性表型。这种相互作用阻止了 miR-590-3p 抑制 APOBEC3G 表达。APOBEC3G 的增加也是人 ESCC 肿瘤中更差临床病理特征的生物标志物。ESCCAL-1 或 APOBEC3G 的耗竭，或 miR-590-3p 的过表达，由于 PI3K/Akt 信号通路的下调，导致细胞凋亡增加。这项研究表明，长链非编码 RNA ESCCAL-1 通过解除 miR-590-3p 对 APOBEC3G 表达的抑制作用，促进 ESCC 的恶性特征，并确定了潜在的生物标志物或治疗靶点，以改善 ESCC 的治疗效果。
