Evidence for an oncogenic role of HOXC6 in human non-small cell lung cancer.

Background: Identification of specific biomarkers is important for the diagnosis and treatment of non-small cell lung cancer (NSCLC). HOXC6 is a homeodomain-containing transcription factor that is highly expressed in several human cancers; however, its role in NSCLC remains unknown.

Methods: The expression and protein levels of were assessed in NSCLC tissue samples by Quantitative real-time PCR (qRT-PCR) and immunohistochemistry, respectively. was transfected into the NSCLC cell lines A549 and PC9, and used to investigate its effect on proliferation, migration, and invasion using CFSE, wound healing, and Matrigel invasion assays. Next-generation sequencing was also used to identify downstream targets of HOXC6 and to gain insights into the molecular mechanisms underlying its biological function.

Results: expression was significantly increased in 66.6% (20/30) of NSCLC tumor samples in comparison to normal controls. HOXC6 promoted proliferation, migration, and invasion of NSCLC cells . RNA-seq analysis demonstrated the upregulation of 310 and 112 genes in A549-HOXC6 and PC9-HOXC6 cells, respectively, and the downregulation of 665 and 385 genes in A549-HOXC6 and PC9-HOXC6 cells, respectively. HOXC6 was also found to regulate the expression of genes such as and , which have documented pro-tumorigenic functions.

Discussion: is highly expressed in NSCLC, and it may enhance lung cancer progression by regulating the expression of pro-tumorigenic genes involved in proliferation, migration, and invasion. Our study highlighted the oncogenic potential of , and suggests that it may be a novel biomarker for the diagnosis and treatment of NSCLC.