Loss of hypermethylated in cancer 1 (HIC1) promotes lung cancer progression

Lung cancer is a leading cause of cancer mortality worldwide with dramatically increasing incidence in recent years. However, the mechanism underlying its progression remains unclear. The aim of this study was to identify the role of hypermethylated in cancer 1 (HIC1) in lung cancer development. Here we found that HIC1 expression was markedly decreased in lung cancer compared with the corresponding adjacent non-cancerous tissues. Meanwhile, overall survival (OS) of lung cancer patients was negatively related with HIC1 expression using TCGA and GEO datasets. Loss of HIC1 expression promoted cell proliferation and migration in vitro. Notable, HIC1 knock-out in Kras^{G12D/+(Lox-Stop-Lox)}/sgHIC1 mice had remarkable effect on tumorigenesis compared with Kras^{G12D/+(Lox-Stop-Lox)}/sgTd control mice. Mechanistic analyses showed that ADAMTS9, DCDC2, FAM46C, ZNF883, F2R, MSH6 and PAX2 genes may be potential downstream targets; DNA repair pathway and transcriptional regulation by TP53 pathway were involved. Finally, this study reveals that HIC1 is associated with lung cancer progression and may provide an effective strategy for its treatment.