化疗耐药仍然是导致肿瘤治疗失败的主要原因，程序性细胞死亡调控失调是引起耐药的重要机理。本课题组前期工作发现，发生化疗耐药的非小细胞肺癌（NSCLC）的细胞焦亡信号存在明显异常。我们通过芯片平台筛选出特异高表达的长链非编码RNA-lncRNA16能够降低NSCLC细胞对于铂类化疗药物的敏感性，可能通过调控细胞焦亡信号，特异miRNAs和STAT3通路途径介导。本课题将在前期工作基础上，研究lncRNA16通过调节细胞焦亡而促进NSCLC化疗耐药的功能；揭示可能的分子调节机制：发挥竞争性内源RNA的作用而抑制miR-1827/miR-1910/miR-6511的调控功能, 增强靶基因DNM1/MBD3甲基化的活性，与STAT3信号相互作用调节炎性小体等；进而探索抑制lncRNA16信号通路抵抗NSCLC化疗耐药的应用价值；此项目有可能为逆转肿瘤耐药提供新的策略和潜在治疗靶点。

Chemoresistance has been still the main reason of therapeutic failure, and dysfunction of programmed cell death regulation is the important mechanism for drug resistance. Our group found significantly abnormity of pyroptosis signaling in the non-small cell lung cancer (NSCLC) with chemoresistance. We used the microassay to find the highly expressed long non-coding RNA (lncRNA)-lncRNA16 in NSCLC tissues. It decreased the sensitivity of chemotherapy that might be related to pyroptosis signaling, specific miRNAs, and STAT3 pathways. Based on our previous data, this project wants to study role of lncRNA16 in regulating pyroptosis that promotes chemoresistance in NSCLC, and reveals the possible mechanisms that lncRNA16 as competitive endogenous RNA may inhibit the function of miR-1827/miR-1910/miR-6511, enhances methylated activity of their targeted genes DNM1/MBD3, and positive effect with STAT3 signaling to regulate inflammatory body et al., and furthermore, it is explored the application value of inhibiting lncRNA16 signaling pathway. This project may provide novel strategy and potentially therapeutic target for reversing tumor drug resistance.