Integrative analysis of non-small cell lung cancer identifies LINC01234 as an oncogenic lncRNA that interacts with HNRNPA2B1 and regulates miR-106b biogenesis

Abstract 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. Down-regulation 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 HNRNPA2B1, which, in turn, led to the recruitment of DGCR8, a subunit of the miRNA microprocessor complex. Accordingly, depletion of either LINC01234 or HNRNPA2B1 reduced the processing of several miRNA precursors, including pri-miR-106b. miR-106b-5p enhanced NSCLC cell growth by downregulating 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.