Long non‐coding RNA ARAP1‐AS1 promotes tumorigenesis and metastasis through facilitating proto‐oncogene c‐Myc translation via dissociating PSF/PTB dimer in cervical cancer

摘要

Long non‐coding RNA (lncRNA) is emerging as a pivotal regulator in tumorigenesis and aggressive progression. Here, we focused on an oncogenic lncRNA, ARAP1 antisense RNA 1 (ARAP1‐AS1), which was notably upregulated in cervical cancer (CC) tissues, cell lines and serum. High ARAP1‐AS1 expression was closely associated with larger tumor size, advanced FIGO stage as well as lymph node metastasis. Importantly, it was identified as an effective diagnostic and prognostic biomarker for CC. In vitro and in vivo assays showed that knockdown of ARAP1‐AS1 inhibited, while overexpression of ARAP1‐AS1 promoted CC cell growth and dissemination. Stepwise mechanistic dissection unveiled that ARAP1‐AS1 could directly interact with PSF to release PTB, resulting in accelerating the internal ribosome entry site (IRES)‐driven translation of proto‐oncogene c‐Myc, thereby facilitating CC development and progression. Moreover, c‐Myc was able to transcriptionally activate ARAP1‐AS1 by directly binding to the E‐box motif located on ARAP1‐AS1 promoter. Taken together, our findings clearly reveal the crucial role of ARAP1‐AS1 in CC tumorigenesis and metastasis via regulation of c‐Myc translation, targeting ARAP1‐AS1 and its related regulatory loop implicates the therapeutic possibility for CC patients.