Ho-Xuan Hung, Lehmann Gerhard, Glazar Petar, Gypas Foivos, Eichner Norbert, Heizler Kevin, Schlitt Hans Jürgen, Zavolan Mihaela, Rajewsky Nikolaus, Meister Gunter, Hackl Christina
Biochemistry Center Regensburg (BCR), Laboratory for RNA Biology, University of Regensburg, 93053 Regensburg, Germany.
Laboratory for Systems Biology of Gene Regulatory Elements, Berlin Institute for Medical Systems Biology, Max-Delbruck Center for Molecular Medicine, 10115 Berlin, Germany.
Cancers (Basel). 2020 Dec 26;13(1):49. doi: 10.3390/cancers13010049.
Understanding the molecular signatures of colorectal cancer progression under chemotherapeutic treatment will be crucial for the success of future therapy improvements. Here, we used a xenograft-based mouse model to investigate, how whole transcriptome signatures change during metastatic colorectal cancer progression and how such signatures are affected by LDM chemotherapy using RNA sequencing. We characterized mRNAs as well as non-coding RNAs such as microRNAs, long non-coding RNAs and circular RNAs in colorectal-cancer bearing mice with or without LDM chemotherapy. Furthermore, we found that circZNF609 functions as oncogene, since over-expression studies lead to an increased tumor growth while specific knock down results in smaller tumors. Our data represent novel insights into the relevance of non-coding and circRNAs in colorectal cancer and provide a comprehensive resource of gene expression changes in primary tumors and metastases. In addition, we present candidate genes that could be important modulators for successful LDM chemotherapy.
了解化疗治疗下结直肠癌进展的分子特征对于未来治疗改进的成功至关重要。在此，我们使用基于异种移植的小鼠模型，通过RNA测序研究转移性结直肠癌进展过程中全转录组特征如何变化，以及这些特征如何受到LDM化疗的影响。我们对接受或未接受LDM化疗的荷结直肠癌小鼠中的mRNA以及非编码RNA（如微小RNA、长链非编码RNA和环状RNA）进行了表征。此外，我们发现circZNF609起着癌基因的作用，因为过表达研究导致肿瘤生长增加，而特异性敲低则导致肿瘤变小。我们的数据代表了对非编码RNA和环状RNA在结直肠癌中的相关性的新见解，并提供了原发性肿瘤和转移灶中基因表达变化的全面资源。此外，我们还提出了可能是LDM化疗成功的重要调节因子的候选基因。
