Recent advances have revealed that lncRNAs play important roles in tumorigenesis. However, only a small number of functional lncRNAs have been well characterized, particularly in colorectal cancer. Therefore, more extensive studies are needed to identify and characterize these lncRNAs to better understand cancer progression. In the present study, using available RNA-seq data, we found that LINC02381 (NR_026656.1) differentially expresses in CRC tissues compared to normal pairs. Consistently, RT-qPCR results showed that LINC02381 was down regulated in CRC tissues and also in different cancerous cell lines. CRC cells treatment with de-methylating and chemotherapy agents indicated that DNA methylation of LINC02381 may be responsible for the transcriptional silencing of LINC02381 in colorectal cancer cells. Then, the functional changes of the cells in response to LINC02381 alteration were assessed and the data indicated that LINC02381 up-regulation suppressed cell viability and proliferation while increasing the apoptosis in CRC-originated cell lines. Mechanistically, LINC02381 overexpression was increased PTEN protein levels but decreased phospho-Akt levels. Finally, we proposed a hypothesized model for PI3K signaling regulation by LINC02381. Altogether, the result of this study suggests that LINC02381 might have suppressive effects on human colorectal cancer tumorigenesis partly by regulating PI3K signaling pathway.

中文翻译：

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表观遗传学上沉默的LINC02381通过调节PI3K-Akt信号传导途径起肿瘤抑制作用。

最近的进展表明，lncRNA在肿瘤发生中起重要作用。然而，仅少数功能性lncRNA已被很好地表征，特别是在结直肠癌中。因此，需要更广泛的研究来鉴定和表征这些lncRNA，以更好地了解癌症的进展。在本研究中，使用可用的RNA序列数据，我们发现LINC02381（NR_026656.1）与正常对相比在CRC组织中差异表达。一致地，RT-qPCR结果显示LINC02381在CRC组织以及不同癌细胞系中均下调。CRC细胞用去甲基化和化学治疗剂处理表明LINC02381的DNA甲基化可能是结直肠癌细胞中LINC02381转录沉默的原因。然后，评估了响应LINC02381改变的细胞功能变化，数据表明LINC02381上调抑制了细胞活力和增殖，同时增加了CRC起源细胞系的凋亡。从机理上讲，LINC02381过表达增加了PTEN蛋白水平，但降低了磷酸化Akt水平。最后，我们提出了LINC02381对PI3K信号进行调控的假设模型。总之，这项研究的结果表明，LINC02381可能部分通过调节PI3K信号通路对人大肠癌的肿瘤发生具有抑制作用。LINC02381过表达增加PTEN蛋白水平，但降低磷酸化Akt水平。最后，我们提出了LINC02381对PI3K信号进行调控的假设模型。总之，这项研究的结果表明，LINC02381可能部分通过调节PI3K信号通路对人大肠癌的肿瘤发生具有抑制作用。LINC02381过表达增加PTEN蛋白水平，但降低磷酸化Akt水平。最后，我们提出了LINC02381对PI3K信号进行调控的假设模型。总而言之，这项研究的结果表明，LINC02381可能部分通过调节PI3K信号通路对人大肠癌的肿瘤发生具有抑制作用。