Although radiotherapy is an essential modality in the treatment of colorectal cancer (CRC), the incidence of radioresistance remains high clinically. Long noncoding RNAs (lncRNAs) reportedly play critical roles in CRC radioresistance by regulating genes or proteins at the transcriptional or post-translational levels. This study aimed to identify novel lncRNAs involved in radioresistance. We found that SP100-AS1 (lncRNA targeting antisense sequence of SP100 gene) was upregulated in radioresistant CRC patient tissues using RNA-seq analysis. Importantly, knockdown of SP100-AS1 significantly reduced radioresistance, cell proliferation, and tumor formation in vitro and in vivo. Mechanistically, mass spectrometry and bioinformatics analyses were used to identify the interacting proteins and microRNAs of SP100-AS1, respectively. Moreover, SP100-AS1 was found to interact with and stabilize ATG3 protein through the ubiquitination-dependent proteasome pathway. In addition, it could serve as a sponge for miR-622, which targeted ATG3 mRNA and affected autophagic activity. Thus, lncRNA SP100-AS1 could act as a radioresistance factor in CRC patients via RNA sponging and protein stabilizing mechanisms. In conclusion, the present study indicates that SP100-AS1/miR-622/ATG3 axis contributes to radioresistance and autophagic activity in CRC patients, suggesting it has huge prospects as a therapeutic target for improving CRC response to radiation therapy.

尽管放疗是治疗结直肠癌 (CRC) 的重要方式，但临床上放射抗性的发生率仍然很高。据报道，长链非编码 RNA (lncRNA) 通过在转录或翻译后水平调节基因或蛋白质，在 CRC 放射抗性中发挥关键作用。本研究旨在鉴定与放射抗性有关的新型 lncRNA。我们发现使用 RNA-seq 分析，SP100-AS1（靶向 SP100 基因反义序列的 lncRNA）在耐辐射 CRC 患者组织中上调。重要的是，SP100-AS1 的敲低显着降低了体外和体内的放射抗性、细胞增殖和肿瘤形成。从机制上讲，质谱和生物信息学分析分别用于鉴定 SP100-AS1 的相互作用蛋白和 microRNA。而且，发现 SP100-AS1 通过泛素化依赖性蛋白酶体途径与 ATG3 蛋白相互作用并稳定 ATG3 蛋白。此外，它还可以作为 miR-622 的海绵，靶向 ATG3 mRNA 并影响自噬活性。因此，lncRNA SP100-AS1 可作为 CRC 患者的放射抗性因子通过RNA 海绵和蛋白质稳定机制。总之，本研究表明 SP100-AS1/miR-622/ATG3 轴有助于 CRC 患者的放射抗性和自噬活性，表明它作为改善 CRC 对放射治疗反应的治疗靶点具有巨大前景。