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A positive feedback loop between AlkB homolog 5 and miR-193a-3p promotes growth and metastasis in esophageal squamous cell carcinoma
Human Cell ( IF 3.4 ) Pub Date : 2020-11-24 , DOI: 10.1007/s13577-020-00458-z
Jinliang Xue 1 , Peng Xiao 1 , Xiangdong Yu 1 , Xiao Zhang 1
Affiliation  

Esophageal squamous cell carcinoma (ESCC) is one of the most frequent malignancies worldwide. miR-193a-3p acts as an oncogene or tumor suppressor in different cancers. However, the functional role and regulatory mechanism of miR-193a-3p in ESCC remain to be elucidated. Our results demonstrated that miR-193a-3p expression was significantly upregulated and associated with advanced TNM stage, recurrence, and poor prognosis in ESCC patients. miR-193-3p targeted ALKBH5 and suppressed its expression. ALKBH5 inhibited miR-193a-3p expression in turn. ALKBH5 affected the primary miR-193a-3p processing by negatively regulating its m6A modification. These findings suggested a positive feedback regulation between miR-193a-3p and ALKBH5 in ESCC cells. Moreover, the functional assays indicated that the miR-193-3p-ALKBH5 feedback loop promoted the proliferation, migration and invasion ability of ESCC cells in vitro, and facilitated tumor growth and metastasis in vivo. Collectively, our current study identified a novel positive feedback regulation between miR-193a-3p and ALKBH5 in ESCC, which may be helpful to gain insight into ESCC pathogenesis and provide novel therapeutic target for ESCC.



中文翻译:

AlkB 同源物 5 和 miR-193a-3p 之间的正反馈回路促进食管鳞状细胞癌的生长和转移

食管鳞状细胞癌 (ESCC) 是全球最常见的恶性肿瘤之一。miR-193a-3p 在不同的癌症中充当癌基因或肿瘤抑制因子。然而,miR-193a-3p 在 ESCC 中的功能作用和调控机制仍有待阐明。我们的结果表明,miR-193a-3p 表达显着上调,并与 ESCC 患者的晚期 TNM 分期、复发和不良预后相关。miR-193-3p 靶向 ALKBH5 并抑制其表达。ALKBH5 依次抑制 miR-193a-3p 的表达。ALKBH5 通过负调节其 m 6影响初级 miR-193a-3p 加工一个修改。这些发现表明在 ESCC 细胞中 miR-193a-3p 和 ALKBH5 之间存在正反馈调节。此外,功能测定表明,miR-193-3p-ALKBH5反馈环在体外促进了ESCC细胞的增殖、迁移和侵袭能力,并促进了体内肿瘤的生长和转移。总的来说,我们目前的研究在 ESCC 中发现了 miR-193a-3p 和 ALKBH5 之间的一种新的正反馈调节,这可能有助于深入了解 ESCC 的发病机制并为 ESCC 提供新的治疗靶点。

更新日期:2020-11-25
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