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高 circ-SEC31A 表达通过调控 miR-520a-5p/GOT-2 轴预测非小细胞肺癌的不良预后。

High circ-SEC31A expression predicts unfavorable prognoses in non-small cell lung cancer by regulating the miR-520a-5p/GOT-2 axis.

机构信息

Shanghai University of Traditional Chinese Medicine, Shanghai University of Medicine and Health Sciences, Shanghai 201203, P.R. China.

Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai 201318, P.R. China.

出版信息

Aging (Albany NY). 2020 Jun 4;12(11):10381-10397. doi: 10.18632/aging.103264.

Abstract

Dysregulation of circular RNAs (circRNAs) has recently been shown to play important regulatory roles in cancer development and progression, including non-small cell lung cancer (NSCLC). However, the roles of most circRNAs in NSCLC are still unknown. In this study, we found that hsa_circ_0001421 (circ-SEC31A) was upregulated in NSCLC tissues and cell lines. Increased circ-SEC31A expression in NSCLC was significantly correlated with malignant characteristics and served as an independent risk factor for the post-surgical overall survival of NSCLC patients. Reduced circ-SEC31A expression in NSCLC decreased tumor cell proliferation, migration, invasion, and malate-aspartate metabolism. Mechanistically, we demonstrated that silencing circ-SEC31A downregulated GOT-2 expression by relieving the sponging effect of miR-520a-5p, which resulted in significantly reduced malate-aspartate metabolism in NSCLC cells. Taken together, these results revealed the important role of circ-SEC31A in the proliferation, migration, invasion, and metabolic regulation of NSCLC cells, providing a new perspective on circRNAs in NSCLC progression.

摘要

环状 RNA(circRNAs)的失调最近被证明在癌症的发展和进展中发挥着重要的调节作用,包括非小细胞肺癌(NSCLC)。然而,大多数 circRNAs 在 NSCLC 中的作用仍然未知。在这项研究中,我们发现 hsa_circ_0001421(circ-SEC31A)在 NSCLC 组织和细胞系中上调。NSCLC 中 circ-SEC31A 的表达增加与恶性特征显著相关,并作为 NSCLC 患者手术后总生存的独立危险因素。在 NSCLC 中降低 circ-SEC31A 的表达可降低肿瘤细胞的增殖、迁移、侵袭和苹果酸-天冬氨酸代谢。从机制上讲,我们证明沉默 circ-SEC31A 通过解除 miR-520a-5p 的海绵效应来下调 GOT-2 的表达,从而导致 NSCLC 细胞中的苹果酸-天冬氨酸代谢显著减少。总之,这些结果揭示了 circ-SEC31A 在 NSCLC 细胞增殖、迁移、侵袭和代谢调控中的重要作用,为 circRNAs 在 NSCLC 进展中的作用提供了新的视角。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8ec/7346017/3f9147da0846/aging-12-103264-g001.jpg

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