b-catenin-mediated upregulation of the ASBEL-TCF3 complex is critical for tumorigenicity of colon cancer cells. Homo sapiens

1. The canonical Wnt/b-catenin signaling pathway plays essential roles in the regulation of the self-renewal of stem and progenitor cells, proliferation, and tumorigenesis of cancer cells. To identify novel genes that are the direct targets of b-catenin in colon cancer cells, we performed RNA-seq and ChIP-seq analysis using DLD-1 cells. 2. We found that b-catenin directly upregulates expression of lncRNA ASBEL. We previously identified ASBEL as an antisense transcript of the ANA/BTG3 gene. We further discovered that ASBEL promotes the tumorigenicity of ovarian cancer cells. ASBEL may inhibit ANA/BTG3 protein expression by forming ASBEL-ANA/BTG3 RNA duplexes, which are retained in the nucleus. ASBEL is required for the tumorigenicity of colon tumor cells. We discovered that knockdown of ASBEL increased the expression of ANA/BTG3 protein in colorectal cancer cells. However, ANA/BTG3 protein levels may not be important for the proliferation of colorectal cancer cells. To elucidate the other potential functions of ASBEL in colorectal cancer cells, we analyzed ASBEL-regulated genes by RNA-seq analysis using HCT116 cells.

1. 经典Wnt/β-连环蛋白信号通路（canonical Wnt/β-catenin signaling pathway）在调控干细胞与祖细胞自我更新、细胞增殖以及癌细胞肿瘤发生过程中发挥不可或缺的关键作用。为鉴定结肠癌细胞中β-连环蛋白的直接靶标新基因，本研究以DLD-1细胞为模型，开展了RNA测序（RNA-seq）与染色质免疫共沉淀测序（ChIP-seq）分析。
2. 研究结果显示，β-连环蛋白可直接上调长链非编码RNA ASBEL（lncRNA ASBEL）的表达。本团队前期已将ASBEL鉴定为ANA/BTG3基因的反义转录本，后续进一步研究发现，ASBEL可通过形成滞留于细胞核内的ASBEL-ANA/BTG3 RNA双链体，抑制ANA/BTG3蛋白的表达。ASBEL对于结肠肿瘤细胞的致瘤性至关重要：本研究证实，敲低ASBEL可提升结直肠癌细胞中ANA/BTG3蛋白的表达水平，但ANA/BTG3蛋白的表达水平或许对结直肠癌细胞的增殖并无显著影响。为阐明ASBEL在结直肠癌细胞中其他潜在的生物学功能，本研究利用HCT116细胞进行RNA测序分析，以筛选ASBEL调控的靶基因。