The discovery of long noncoding RNAs (lncRNAs) has increased our understanding of the development and progression of many cancers, but their contributions to non-small cell lung cancer (NSCLC) remain poorly understood. Here, we profiled lncRNA expression in NSCLC and investigated in detail the molecular function of one upregulated lncRNA, LINC01234. LINC01234 was overexpressed in NSCLC compared with normal lung tissue and correlated positively with poor prognosis. Downregulation of LINC01234 impaired cell proliferation in vitro and tumor growth in vivo. RNA pull-down/mass spectrometry experiments showed that LINC01234 interacted with the RNA-binding protein heterogeneous nuclear ribonucleoprotein A2/B1 (HNRNPA2B1), which, in turn, led to the recruitment of DiGeorge syndrome critical region gene 8 (DGCR8), a subunit of the microRNA (miRNA) microprocessor complex. Accordingly, depletion of either LINC01234 or HNRNPA2B1 reduced the processing of several miRNA precursors, including primary microRNA (pri-miR)-106b. miR-106b-5p enhanced NSCLC cell growth by downregulating cryptochrome 2 (CRY2), thereby increasing c-Myc expression. Finally, we found that activated c-Myc binds to the LINC01234 promoter to increase its transcription, creating a c-Myc–LINC01234–HNRNPA2B1–miR-106b-5p–CRY2–c-Myc positive-feedback loop. We identified numerous lncRNAs with dysregulated expression in NSCLC and demonstrated a novel oncogenic axis involving LINC01234, HNRNPA2B1, miR-106b-5p, CRY2, and c-Myc. Components of this axis may be potential novel targets for NSCLC.

长非编码RNA（lncRNA）的发现增加了我们对许多癌症的发生和发展的了解，但对非小细胞肺癌（NSCLC）的贡献仍然知之甚少。在这里，我们分析了lncRNA在NSCLC中的表达，并详细研究了一个上调的lncRNA LINC01234的分子功能。与正常肺组织相比，LINC01234在NSCLC中过表达，并且与不良预后呈正相关。下调LINC01234损害体外细胞增殖和体内肿瘤生长。RNA下拉/质谱实验表明LINC01234与RNA结合蛋白异质核糖核蛋白A2 / B1（HNRNPA2B1）相互作用，进而导致募集了DiGeorge综合征关键区域基因8（DGCR8），是microRNA（miRNA）微处理器复合体的亚基。因此，LINC01234或HNRNPA2B1的消耗减少了几种miRNA前体的加工，包括初级microRNA（pri-miR）-106b。miR-106b-5p通过下调隐色素2（CRY2）增强NSCLC细胞的生长，从而增加c-Myc的表达。最后，我们发现激活的c-Myc与LINC01234启动子结合以增加其转录，从而形成c-Myc–LINC01234–HNRNPA2B1–miR-106b-5p–CRY2–c-Myc正反馈环。我们鉴定了在NSCLC中表达失调的许多lncRNA，并证明了涉及LINC01234，HNRNPA2B1，miR-106b-5p，CRY2和c-Myc的新型致癌轴。该轴的成分可能是NSCLC的潜在新靶标。