No abstract

Pancreatic cancer (PC) is one of the deadliest malignancies, with poor diagnosis and prognosis.miR-532-3phas been reported to be a tumor suppressor in various cancers, whereas the mechanism ofmiR-532-3pin the progression of PC remains poorly understood. In this study, it was found thatmiR-532-3pandSOCS2were down-regulated, whereasDNMT3Awas up-regulated in PC. Knockdown ofDNMT3Aor overexpression ofmiR-532-3psuppressed PC cell proliferation, invasion, and migration, as well as tumor formation in nude mice. DNMT3A induced the methylation ofSOCS2promoter.SOCS2knockdown reversed the inhibiting effect ofDNMT3Asilencing on PC cell growth.miR-532-3pdirectly bound toDNMT3Aand negatively regulated its expression while up-regulatingSOCS2levels.DNMT3Aoverexpression reversed the inhibiting effect ofmiR-532-3poverexpression on PC cell growth. In conclusion, the overexpression ofmiR-532-3pcould suppress proliferation, invasion, and migration of PC cells, as well as tumor formation in nude mice through inhibiting the methylation ofSOCS2by targetingDNMT3A.

Backgound Pancreatic cancer (PC) is one of the deadliest cancers worldwide, and cell proliferation and angiogenesis play an important role in its occurrence and development. High levels of lncRNANORAD have been detected in many tumors, including PC, yet the effect and mechanism of lncRNA NORAD on PC cell angiogenesis are unexplored. Methods qRT.PCR was applied to quantify lncRNA NORAD and miR-532-3p expression in PC cells, and a dual luciferase reporter gene was used to verify the targeting effects of NORAD, miR-532-3p and Nectin-4. Then, we regulated NORAD and miR-532-3p expression in PC cells and detected their effects on PC cell proliferation and angiogenesis using cloning experiments and HUVEC tube formation experiments. Results LncRNA NORAD was upregulated and miR-532-3p was downregulated in PC cells compared with normal cells. Knockdown of NORAD inhibited PC cell proliferation and angiogenesis. LncRNA NORAD and miR-532-3p competitively bound to promote the expression of the miR-532-3p target gene Nectin-4, thereby promoting proliferation and angiogenesis of PC cells in vitro. Conclusion LncRNA NORAD promotes the proliferation and angiogenesis of PC cells by regulating the miR-532-3p/Nectin-4 axis, which may be a potential biological target in the diagnosis and treatment of clinical PC.