坏死程序性死亡（Necroptosis）是一种受控的坏死形式，当细胞缺乏凋亡信号时可以被激活。DR家族配体和各种细胞内外刺激也可诱导坏死程序性死亡的激活。特异性的RIP1拮抗剂坏死素抑制剂可以通过抑制RIP1激酶来预防坏死程序性死亡，从而允许在DR配体存在的情况下细胞存活和扩展。此外，有越来越多的证据表明，长链非编码RNA（lncRNA）分子在细胞死亡过程中如凋亡、自噬、火山爆发和坏死程序性死亡方面发挥着重要作用。因此，这里旨在揭示参与坏死程序性死亡信号的调控和维持的lncRNA。为此，研究使用结肠癌细胞系HT-29和HCT-116。通过化学调节坏死程序性死亡信号，使用5-氟尿嘧啶、TNF-α和/或坏死素-1进行实验。通过实时荧光定量PCR测定基因表达水平。注意到，lncRNA P50相关COX-2非基因型RNA（PACER）在坏死程序性死亡诱导的结肠癌中受到抑制，而当坏死程序性死亡被抑制时，PACER的表达得到恢复。此外，HCT-116结肠癌细胞没有观察到明显的变化，因为这些细胞缺乏RIP3激酶的表达。总的来说，当前研究结果明确地表明，PACER在控制坏死程序性死亡的信号传递中具有关键的调节作用。值得注意的是，PACER的肿瘤促进作用可能是导致癌细胞缺乏坏死程序性死亡信号的原因。此外，RIP3激酶似乎是PACER相关坏死程序性死亡的必要成分。© 2023。作者（们），在Springer Nature B.V.独家许可下。

Necroptosis is a controlled form of necrosis which can be stimulated in cases where the apoptosis signal is absent. Necroptosis can be induced by DR family ligands and by various intracellular and extracellular stimuli that triggers the activation of DR family ligands. Necrostatins, which are specific RIP1 antagonists, prevent necroptosis by inhibiting RIP1 kinase, allowing survival and propagation of cells in the presence of DR ligands. Furthermore, there is a mounting evidence that long non-coding RNA (lncRNA) molecules accomplish vital functions in cell death processes such as apoptosis, autophagy, pyroptosis, and necroptosis. Accordingly, here we aimed to decipher the lncRNAs that are involved in the control and maintenance of necroptosis signaling.Colon cancer cell lines, HT-29 and HCT-116 were used for the study. For the chemical modulation of necroptosis signaling, 5-Fluorouracil, TNF-α and/or Necrostatin-1 were used. Gene expression levels were determined by quantitative real-time PCR. Remarkably, lncRNA P50-associated COX-2 extragenic RNA (PACER) was identified to be suppressed in necroptosis-induced colon cancers, whereas the expression of PACER was restored when necroptosis was suppressed. In addition, no detectable change was observed in HCT-116 colon cancer cells, as these cells lack the expression of RIP3 kinase.Collectively, current findings clearly imply that PACER have key regulatory roles in the control of necroptotic cell death signaling circuitry. Notably, the tumor promoter activity of PACER might be responsible for the lack of necroptotic death signal in cancer cells. Also, RIP3 kinase seems to be essential component in PACER-associated necroptosis.© 2023. The Author(s), under exclusive licence to Springer Nature B.V.