SLCO4A1-AS1-202通过调控细胞糖代谢重编程促进肺腺癌恶性表型

肿瘤细胞的糖酵解能力较正常细胞明显提高，这种代谢特点与其细胞恶性表型密切相关，故探索肿瘤细胞糖代谢的分子机制具有重要的意义。我们发现一个在肺腺癌（LAD）细胞糖代谢中发挥重要调控作用的长链非编码RNA，SLCO4A1-AS1-202。前期预实验表明SLCO4A1-AS1-202在LAD中表达升高且与患者预后相关。SLCO4A1-AS1-202在胞浆和胞核中都有分布并能调控糖酵解进而促进LAD细胞增殖侵袭。初步实验表明其在胞浆中通过结合EGFR和PFKP，促进EGFR磷酸化PFKP，进而使Akt通路激活；同时在胞核中通过作为转录因子c-Myc的辅因子，促进LDHA的转录，从而导致LAD细胞更多利用糖酵解为细胞供能。以这些为基础，本项目将系统性地研究SLCO4A1-AS1-202调控糖酵解在诱导LAD细胞增殖及侵袭转移中的重要作用及分子机理，为LAD的治疗寻找可能新靶点。

Reprogramming of cellular metabolism is a hallmark of cancers and cancer cells more readily use glycolysis. Understanding the mechanisms involved in the process of glucose metabolism is a major challenge in cancer research. In lung adenocarcinoma (LAD), we found an important glycolysis-related long non-coding RNA, SLCO4A1-AS1-202. Preliminary experiments showed that SLCO4A1-AS1-202 located both in cytoplasmic and nuclear fractions. We found that SLCO4A1-AS1-202 functioned as a scaffold in the cytoplasm, it promotes the interaction between EGFR and PFKP and thus the phosphorylation of PFKP, which subsequently activated Akt signaling. Meanwhile, SLCO4A1-AS1-202 acts as a transcriptional coactivator of c-Myc, thereby promoting LDHA transcription. The roles of SLCO4A1-AS1-202 in cytoplasm and nucleus can work together to promote glycolysis, which in turn facilitates the malignant phenotypes of the LAD cells. We will systematically research how SLCO4A1-AS1-202 regulates glycolysis activity in the induction of LAD malignant phenotypes, which may put new insight into the therapeutic strategies for LAD.