HOXD9 Stimulates the Process of Colorectal Carcinoma by Regulating KLK9

Abstract

Colorectal carcinoma (CRC) is a common tumor in the digestive system. This study aims to elucidate the possible relationship between abnormally expressed HOXD9 and the malignant process of CRC. HOXD9 levels were analyzed in CRC and adjacent non-tumoral tissues to evaluate its prognostic value in CRC patients. Knockdown of HOXD9 was performed, and the proliferative and migratory capacities of LoVo and LS513 cells were assessed using CCK-8, transwell, and wound healing assays. Bioinformatic analysis and dual-luciferase reporter assay revealed the interaction between HOXD9 and KLK9. Rescue experiments were conducted to elucidate the co-regulation of HOXD9 and KLK9 on CRC cell behaviors. HOXD9 was upregulated in CRC tissues, and high level of HOXD9 predicted poor prognosis in CRC patients. HOXD9 was identically upregulated in CRC cell lines, especially LoVo and LS513 cells, which were used for generating HOXD9 knockdown models by transfection of sh-HOXD9. Knockdown of HOXD9 weakened proliferative and migratory capacities in CRC cells. KLK9 was the target binding HOXD9, which was downregulated in CRC tissues and cell lines. Knockdown of KLK9 reversed the inhibited proliferative and migratory capacities in CRC cells owing to HOXD9 knockdown. Highly expressed HOXD9 in CRC tissues is closely linked to the prognosis. HOXD9 stimulates CRC cells to proliferate and migrate by upregulating KLK9.