PAX5-induced upregulation of IDH1-AS1 promotes tumor growth in prostate cancer by regulating ATG5-mediated autophagy.

Prostate cancer (PCa) is one of the major malignancies affecting males' health around the world. Long noncoding RNAs (lncRNAs), a class of long transcripts, has been reported as essential regulators in tumorigenesis. IDH1 antisense RNA 1 (IDH1-AS1) is an lncRNA which can interact with genes to regulate the Warburg effect. However, function and mechanism of it in tumorigenesis of PCa remains unclear. Therefore, our current study focused on exploring the role of IDH1-AS1 in PCa tumor growth. At first, the expression of IDH1-AS1 was identified to be upregulated in PCa samples and cell lines. Mechanism associated with the upregulation of IDH1-AS1 was analyzed and demonstrated by mechanism experiments. The result suggested that PAX5 is the transcriptional activator of IDH1-AS1. Functionally, loss-of function assays revealed that silencing of IDH1-AS1 inhibited cell proliferation and induced cell apoptosis both in vitro and in vivo. Through microarray analysis and Gene ontology (GO) analysis, we determined that IDH1-AS1 can affect PCa cell autophagy by upregulating ATG5 expression. Mechanism investigation further validated that IDH1-AS1 posttranscriptionally regulated ATG5 expression by enhancing the mRNA stability of ATG5 or upregulating ATG5 by sequestering miR-216b-5p. Consequently, rescue assays demonstrated that IDH1-AS1 promoted proliferation and apoptosis in PCa via ATG5-induced autophagy. Taken together, our study elucidated the function and regulatory mechanism of IDH1-AS1, thus providing a novel biomarker for PCa.

KEYWORDS: {{ getKeywords(articleDetailText.words) }}