Department of Thoracic Surgery, The Second Hospital of Shandong University, Jinan, China.
Key Laboratory of Chest Cancer, Shandong University, The Second Hospital of Shandong University, Jinan, China.
Cancer Sci. 2023 Jul;114(7):2835-2847. doi: 10.1111/cas.15807. Epub 2023 Apr 17.
Circular RNAs (circRNAs) play a pivotal role in the tumorigenesis and progression of various cancers. However, the role and mechanisms of circABCA13 in esophageal squamous cell carcinoma (ESCC) are largely unknown. Here, we reported that circABCA13, a novel circular RNA generated by back-splicing of the intron of the ABCA13 gene, is highly expressed in ESCC tumor tissues and cell lines. Upregulation of circABCA13 correlated with TNM stage and a poor prognosis in ESCC patients. While knockdown of circABCA13 in ESCC cells significantly reduced cell proliferation, migration, invasion, and anchorage-independent growth, overexpression of circABCA13 facilitated tumor growth both in vitro and in vivo. In addition, circABCA13 directly binds to miR-4429 and sequesters miR-4429 from its endogenous target, SRXN1 mRNA, which subsequently upregulates SRXN1 and promotes ESCC progression. Consistently, overexpression of miR-4429 or knockdown of SRXN1 abolished malignant behavior promotion of ESCC results from circABCA13 overexpression in vitro and in vivo. Collectively, our study uncovered the oncogenic role of circABCA13 and its mechanism in ESCC, suggesting that circABCA13 could be a potential therapeutic target and a predictive biomarker for ESCC patients.
环状 RNA(circRNAs)在多种癌症的发生和发展中起着关键作用。然而,circABCA13 在食管鳞状细胞癌(ESCC)中的作用和机制在很大程度上尚不清楚。在这里,我们报道了 circABCA13,一种由 ABCA13 基因内含子反向剪接产生的新型环状 RNA,在 ESCC 肿瘤组织和细胞系中高度表达。circABCA13 的上调与 ESCC 患者的 TNM 分期和预后不良相关。而在 ESCC 细胞中敲低 circABCA13 显著降低了细胞增殖、迁移、侵袭和无锚定生长能力,而过表达 circABCA13 则促进了体外和体内的肿瘤生长。此外,circABCA13 可直接与 miR-4429 结合,并将 miR-4429 从其内源性靶标 SRXN1 mRNA 上隔离出来,从而上调 SRXN1 并促进 ESCC 进展。一致地,过表达 miR-4429 或敲低 SRXN1 可消除体外和体内 circABCA13 过表达对 ESCC 恶性行为的促进作用。总之,我们的研究揭示了 circABCA13 在 ESCC 中的致癌作用及其机制,表明 circABCA13 可能是 ESCC 患者的潜在治疗靶点和预测生物标志物。