Division of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea.
Department of Radiological and Medico-Oncological Sciences, University of Science and Technology, Daejeon 34113, Republic of Korea.
Int J Mol Sci. 2023 Jan 4;24(2):978. doi: 10.3390/ijms24020978.
Precise prediction of radioresistance is an important factor in the treatment of colorectal cancer (CRC). To discover genes that regulate the radioresistance of CRCs, we analyzed an RNA sequencing dataset of patient-originated samples. Among various candidates, IGFL2-AS1, a long non-coding RNA (lncRNA), exhibited an expression pattern that was well correlated with radioresistance. IGFL2-AS1 is known to be highly expressed in various cancers and functions as a competing endogenous RNA. To further investigate the role of IGFL2-AS1 in radioresistance, which has not yet been studied, we assessed the amount of IGFL2-AS1 transcripts in CRC cell lines with varying degrees of radioresistance. This analysis showed that the more radioresistant the cell line, the higher the level of IGFL2-AS1 transcripts-a similar trend was observed in CRC samples. To directly assess the relationship between IGFL2-AS1 and radioresistance, we generated a CRC cell line stably expressing a small hairpin RNA (shRNA) targeting IGFL2-AS1. shRNA-mediated knockdown of IGFL2-AS1 decreased radioresistance and cell migration in vitro, establishing a functional role for IGFL2-AS1 in radioresistance. We also showed that downstream effectors of the AKT pathway played crucial roles. These data suggest that IGFL2-AS1 contributes to the acquisition of radioresistance by regulating the AKT pathway.
精确预测肿瘤的放射抵抗性是结直肠癌(CRC)治疗的一个重要因素。为了发现调控CRC 放射抵抗性的基因,我们分析了患者来源样本的 RNA 测序数据集。在各种候选基因中,IGFL2-AS1,一种长非编码 RNA(lncRNA),其表达模式与放射抵抗性密切相关。IGFL2-AS1 在各种癌症中表达水平较高,并且作为竞争内源性 RNA 发挥作用。为了进一步研究 IGFL2-AS1 在放射抵抗性中的作用,我们评估了具有不同放射抵抗性的 CRC 细胞系中 IGFL2-AS1 转录本的含量。该分析表明,细胞系的放射抵抗性越高,IGFL2-AS1 转录本的水平越高——在 CRC 样本中也观察到了类似的趋势。为了直接评估 IGFL2-AS1 与放射抵抗性之间的关系,我们生成了一种稳定表达靶向 IGFL2-AS1 的短发夹 RNA(shRNA)的 CRC 细胞系。shRNA 介导的 IGFL2-AS1 敲低降低了体外的放射抵抗性和细胞迁移,确立了 IGFL2-AS1 在放射抵抗性中的功能作用。我们还表明,AKT 通路的下游效应物发挥了关键作用。这些数据表明,IGFL2-AS1 通过调节 AKT 通路促进放射抵抗性的获得。