• Sixian Chen, Qingyun Zhao, Ruirui Zhang, Jungang Liu, Wenyi Peng, Haotian Xu, Xiaofei Li, Xin Wang, Shuilian Wu, Gang Li, and Aruo Nan.
• School of Public Health, Guangxi Medical University, Nanning 530021, PR China; Guangxi Key Laboratory of Environment and Health Research, Guangxi Medical University, Nanning 530021, PR China.
• Transl Res. 2024 Aug 1; 270: 526552-65.

AbstractThe transcribed ultraconserved region (T-UCR) belongs to a new type of lncRNAs that are conserved in homologous regions of the rat, mouse and human genomes. A lot of research has reported that differential expression of T-UCRs can influence the development of various cancers, revealing the ability of T-UCRs as new therapeutic targets or potential cancer biomarkers. Most studies on the molecular mechanisms of T-UCRs in cancer have focused on ceRNA regulatory networks and interactions with target proteins, but the present study reveals an innovative dual-targeted regulatory approach in which T-UCRs bind directly to mRNAs and directly to proteins. We screened T-UCRs that may be related to colorectal cancer (CRC) by performing a whole-genome T-UCR gene microarray and further studied the functional mechanism of T-UCR uc.285+ in the development of CRC. Modulation of uc.285+ affected the proliferation of CRC cell lines and influenced the expression of the CDC42 gene. We also found that uc.285+ promoted the proliferation of CRC cells by directly binding to CDC42 mRNA and enhancing its stability while directly binding to CDC42 protein and affecting its stability. In short, our research on the characteristics of cell proliferation found that uc.285+ has a biological function in promoting CRC proliferation. uc.285+ may have considerable potential as a new diagnostic biomarker for CRC.Copyright © 2024 Elsevier Inc. All rights reserved.

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