Department of Thoracic Surgery, Luoyang Central Hospital Affiliated To Zhengzhou University, No.288, Zhongzhou Middle Road, Luoyang City, 471009, Henan Province, China.
Hum Cell. 2021 Mar;34(2):502-514. doi: 10.1007/s13577-020-00458-z. Epub 2020 Nov 24.
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 mA 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.
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 中的功能作用和调节机制仍有待阐明。我们的研究结果表明，miR-193a-3p 的表达在 ESCC 患者中显著上调，并与晚期 TNM 分期、复发和不良预后相关。miR-193a-3p 靶向 ALKBH5 并抑制其表达。ALKBH5 反过来抑制 miR-193a-3p 的表达。ALKBH5 通过负调控其 mA 修饰来影响初级 miR-193a-3p 的加工。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 反馈环促进了 ESCC 细胞在体外的增殖、迁移和侵袭能力，并促进了体内肿瘤的生长和转移。总之，我们目前的研究在 ESCC 中鉴定了 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。
