J Cancer 2021; 12(21):6439-6444. doi:10.7150/jca.62631

Research Paper

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

Xiaoli Zhang, Hongbo Zhu, Xiaoguang Qu, Ziying Yu, Jing Zhang

The First Affiliated Hospital, Department of Pathology, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China.

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Zhang X, Zhu H, Qu X, Yu Z, Zhang J. Suppressing LncRNA HOXA-AS3 by CRISPR-dCas9 inhibits pancreatic cancer development. J Cancer 2021; 12(21):6439-6444. doi:10.7150/jca.62631. Available from https://www.jcancer.org/v12p6439.htm

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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.

Keywords: lncRNA HOXA-AS3, CRISPR-dCas9, pancreatic cancer, miR-29c, CDK6