Aberrations in Capicua (CIC) have recently been implicated as a negative prognostic factor in a multitude of cancer types through activation of the MAPK signalling cascade and derepression of oncogenic ETS transcription factors. The Ataxin-family protein ATXN1L has previously been reported to interact with CIC in developmental and disease contexts to facilitate the repression of CIC target genes. To further investigate this relationship, we performed functional in vitro studies utilizing ATXN1L^KO and CIC^KO human cell lines and characterized a reciprocal functional relationship between CIC and ATXN1L. Transcriptomic interrogation of the CIC-ATXN1-ATXN1L axis in low-grade glioma, prostate adenocarcinoma and stomach adenocarcinoma TCGA cohorts revealed context-dependent convergence of gene sets and pathways related to mitotic cell cycle and division. This study highlights the CIC-ATXN1-ATXN1L axis as a more potent regulator of the cell cycle than previously appreciated.

中文翻译：

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CIC 和 ATXN1L 的转录组学分析揭示了癌症利用的功能关系。

Capicua (CIC) 畸变最近被认为是多种癌症类型的负面预后因素，通过激活 MAPK 信号级联和致癌 ETS 转录因子的去抑制。Ataxin 家族蛋白 ATXN1L 以前曾被报道在发育和疾病背景下与 CIC 相互作用，以促进 CIC 靶基因的抑制。为了进一步研究这种关系，我们利用 ATXN1L ^KO和 CIC ^KO进行了功能体外研究人类细胞系，并表征了 CIC 和 ATXN1L 之间的相互功能关系。低级别胶质瘤、前列腺腺癌和胃腺癌 TCGA 队列中 CIC-ATXN1-ATXN1L 轴的转录组学研究揭示了与有丝分裂细胞周期和分裂相关的基因集和通路的上下文依赖性收敛。这项研究强调了 CIC-ATXN1-ATXN1L 轴是比以前认为的更有效的细胞周期调节剂。