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Background  Oct4, a key stemness transcription factor, is overexpressed in lung cancer. Here, we reveal a novel transcription regulation of long non-coding RNAs (lncRNAs) by Oct4. LncRNAs have emerged as important players in cancer progression.    Methods  Oct4 chromatin-immunoprecipitation (ChIP)-sequencing and several lncRNA databases with literature annotation were integrated to identify Oct4-regulated lncRNAs. Luciferase activity, qRT-PCR and ChIP-PCR assays were conducted to examine transcription regulation of lncRNAs by Oct4. Reconstitution experiments of Oct4 and downstream lncRNAs in cell proliferation, migration and invasion assays were performed to confirm the Oct4-lncRNAs signaling axes in promoting lung cancer cell growth and motility. The expression correlations between Oct4 and lncRNAs were investigated in 124 lung cancer patients using qRT-PCR analysis. The clinical significance of Oct4/lncRNAs signaling axes were further evaluated using multivariate Cox regression and Kaplan-Meier analyses.    Results  We confirmed that seven lncRNAs were upregulated by direct binding of Oct4. Among them,  nuclear paraspeckle assembly transcript 1  ( NEAT1 ),  metastasis-associated lung adenocarcinoma transcript 1  ( MALAT1 ) and  urothelial carcinoma-associated 1  ( UCA1 ) were validated as Oct4 transcriptional targets through promoter or enhancer activation. We showed that lung cancer cells overexpressing  NEAT1  or  MALAT1  and the Oct4-silenced cells reconstituted with  NEAT1  or  MALAT1  promoted cell proliferation, migration and invasion. In addition, knockdown of  NEAT1  or  MALAT1  abolished Oct4-mediated lung cancer cell growth and motility. These cell-based results suggested that Oct4/ NEAT1  or Oct4/ MALAT1  axis promoted oncogenesis .  Clinically, Oct4/ NEAT1 / MALAT1  co-overexpression was an independent factor for prediction of poor outcome in 124 lung cancer patients.    Conclusions  Our study reveals a novel mechanism by which Oct4 transcriptionally activates  NEAT1  via promoter and  MALAT1  via enhancer binding to promote cell proliferation and motility, and led to lung tumorigenesis and poor prognosis.    Electronic supplementary material  The online version of this article (doi:10.1186/s12943-017-0674-z) contains supplementary material, which is available to authorized users.

Oct4 transcriptionally regulates the expression of long non-coding RNAs NEAT1 and MALAT1 to promote lung cancer progression