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Background  The biology function of antisense intronic long noncoding RNA (Ai-lncRNA) is still unknown. Meanwhile, cancer patients with paclitaxel resistance have limited therapeutic options in the clinic. However, the potential involvement of Ai-lncRNA in paclitaxel sensitivity remains unclear in human cancer.    Methods  Whole transcriptome sequencing of 33 breast specimens was performed to identify Ai-lncRNA  EGOT . Next, the role of  EGOT  in regulation of paclitaxel sensitivity was investigated. Moreover, the mechanism of  EGOT  enhancing autophagy sensitizes paclitaxel cytotoxicity via upregulation of ITPR1 expression by RNA-RNA and RNA-protein interactions was investigated in detail. Furthermore, upstream transcriptional regulation of  EGOT  expression was also investigated by co-immunoprecipitation and chromatin immunoprecipitation. Finally, clinical breast specimens in our cohort, TCGA and ICGC were applied to validate the role of  EGOT  in enhancing of paclitaxel sensitivity.    Results   EGOT  enhances autophagosome accumulation via the up-regulation of ITPR1 expression, thereby sensitizing cells to paclitaxel toxicity. Mechanistically, on one hand,  EGOT  upregulates ITPR1 levels via formation of a  pre-ITPR1/EGOT  dsRNA that induces  pre-ITPR1  accumulation to increase ITPR1 protein expression  in cis . On the other hand,  EGOT  recruits hnRNPH1 to enhance the alternative splicing of pre-ITPR1  in trans  via two binding motifs in  EGOT  segment 2 (324–645 nucleotides) in exon 1. Moreover,  EGOT  is transcriptionally regulated by stress conditions. Finally,  EGOT  expression enhances paclitaxel sensitivity via assessment of cancer specimens.    Conclusions  These findings broaden comprehensive understanding of the biology function of Ai-lncRNAs. Proper regulation of  EGOT  may be a novel synergistic strategy for enhancing paclitaxel sensitivity in cancer therapy.    Electronic supplementary material  The online version of this article (10.1186/s12943-019-1017-z) contains supplementary material, which is available to authorized users.

molecular cancer

Ai-lncRNA EGOT enhancing autophagy sensitizes paclitaxel cytotoxicity via upregulation of ITPR1 expression by RNA-RNA and RNA-protein interactions in human cancer