Research Center for Functional Genomics Biomedicine and Translational Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania.
Department of Translational Molecular Pathology, Division of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Int J Mol Sci. 2021 Nov 19;22(22):12491. doi: 10.3390/ijms222212491.
Colon cancer-associated transcript 2 (CCAT2) is an intensively studied lncRNA with important regulatory roles in cancer. As such, cumulative studies indicate that CCAT2 displays a high functional versatility due to its direct interaction with multiple RNA binding proteins, transcription factors, and other species of non-coding RNA, especially microRNA. The definitory mechanisms of CCAT2 are its role as a regulator of the TCF7L2 transcription factor, enhancer of MYC expression, and activator of the WNT/β-catenin pathway, as well as a role in promoting and maintaining chromosome instability through the BOP1-AURKB pathway. Additionally, we highlight how the encompassing rs6983267 SNP has been shown to confer CCAT2 with allele-specific functional and structural particularities, such as the allelic-specific reprogramming of glutamine metabolism. Additionally, we emphasize CCAT2's role as a competitive endogenous RNA (ceRNA) for multiple tumor suppressor miRNAs, such as miR-4496, miR-493, miR-424, miR-216b, miR-23b, miR-34a, miR-145, miR-200b, and miR-143 and the pro-tumorigenic role of the altered regulatory axis. Additionally, due to its upregulation in tumor tissues, wide distribution across cancer types, and presence in serum samples, we outline CCAT2's potential as a biomarker and disease indicator and its implications for the development of resistance against current cancer therapy regiments and metastasis.
结肠癌相关转录物 2（CCAT2）是一种备受关注的长非编码 RNA，在癌症中具有重要的调控作用。因此，大量研究表明，CCAT2 由于其与多种 RNA 结合蛋白、转录因子和其他非编码 RNA（尤其是 microRNA）的直接相互作用，表现出高度的多功能性。CCAT2 的定义机制是作为 TCF7L2 转录因子、MYC 表达增强子和 WNT/β-catenin 通路激活剂的调节剂，以及通过 BOP1-AURKB 通路促进和维持染色体不稳定性的作用。此外，我们强调了 rs6983267 单核苷酸多态性如何赋予 CCAT2 具有等位基因特异性的功能和结构特性，例如谷氨酰胺代谢的等位基因特异性重编程。此外，我们强调了 CCAT2 作为多个肿瘤抑制 miRNA（如 miR-4496、miR-493、miR-424、miR-216b、miR-23b、miR-34a、miR-145、miR-200b 和 miR-143）的竞争性内源性 RNA（ceRNA）的作用，以及改变的调节轴的促肿瘤作用。此外，由于其在肿瘤组织中的上调、在多种癌症类型中的广泛分布以及在血清样本中的存在，我们概述了 CCAT2 作为生物标志物和疾病指标的潜力及其对当前癌症治疗方案和转移耐药性发展的影响。
