Long non-coding RNA ESCCAL-1 promotes esophageal squamous cell carcinoma by down regulating the negative regulator of APOBEC3G
Long non-coding RNA ESCCAL-1 promotes esophageal squamous cell carcinoma by down regulating the negative regulator of APOBEC3G
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DOI：
10.1016/j.canlet.2020.09.001
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发表时间：
2020-11-28
期刊：
影响因子：
9.7
通讯作者：
Cao, Wei
中科院分区：
文献类型：
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作者：
Liu, Jia;Mayekar, Manasi K.;Cao, Wei
食管鳞状细胞癌（ESCC）中lncRNA ESCCAL-1的表达上调。然而，食管癌中ESCCAL-1调控的分子途径仍然不清楚。我们发现lncRNA 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，ESCC模型中ESCCAL-1的耗竭抑制了与恶性肿瘤相关的细胞过程，包括增殖、迁移和侵袭、抗凋亡和小鼠肿瘤生长受损。使用组合方法，我们发现ESCCAL-1通过充当miR-590- 3 p的分子海绵来调节ESCC中的恶性表型。这种相互作用阻止miR-590- 3 p抑制APOBEC 3G表达。APOBEC 3G增加也是人ESCC肿瘤中更差临床病理特征的生物标志物。ESSCAL-1或APOBEC 3G的缺失或miR-590- 3 p的过表达由于PI 3 K/Akt信号转导的下调而导致细胞凋亡增加。这项研究表明，lncRNA ESCCAL-1通过减轻miR-590- 3 p对APOBEC 3G表达的抑制作用促进了ESCC的恶性特征，并确定了改善ESCC治疗结果的潜在生物标志物或治疗靶点。
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.