Suppressing LncRNA HOXA-AS3 by CRISPR-dCas9 inhibits pancreatic cancer development

The lncRNA HOXA-AS3 has been reported as a potential oncogene in tumors. Nevertheless, the molecular mechanism of HOXA-AS3 in pancreatic cancer (PC) progression remains unknown. We performed quantitative real-time (qRT) PCR assay to detect the expression levels of HOXA-AS3, miR-29c in PC specimens. Then, we transfected sgRNA-HOXA-AS3, miR-29c mimics, miR-29c inhibitors, or vector-CDK6 plasmids into PC cell lines to regulate the expression levels of HOXA-AS3, miR-29c or CDK6. Luciferase reporter assay was performed to identify the correlations among miR-29c, HOXA-AS3 and 3' UTR of CDK6.The ability of cell proliferation was assessed by cell counting and subcutaneous tumor growth assay. HOXA-AS3 level was upregulated in PC, and its knockdown suppressed PC cells proliferation, whereas miR-29c antagonized the regulatory effect of HOXA-AS3 knockdown by directly binding to HOXA-AS3.Moreover, CDK6 was a target of miR-29c and miR-29c exerted anti-proliferation effects through inhibiting CDK6. HOXA-AS3 could accelerate the growth of PC cells partially by regulating the miR-29c/CDK6 axis, which could be used as a potential therapeutic target in CRISPR-mediated PC treatment.