HOXC10 promotes cell migration, invasion, and tumor growth in gastric carcinoma cells through upregulating proinflammatory cytokines

Abstract

HOXC10 plays a critical role in many cellular processes, such as proliferation, migration, and invasion, but the function of HOXC10 in gastric carcinoma is not clear.In this study, we aimed to investigate the expression profile of HOXC10 and its role in gastric carcinoma cells and in vivo experiments. HOXC10 expression patterns were detected in clinical samples and gastric cancer cells lines by reverse transcriptase polymerase chain reaction assays, and then, we focused on its role in regulating cell proliferation, cell cycle, migration, and invasion after transfection of silencing and overexpression plasmids in vitro and in vivo. Finally, we confirmed the correlation between HOXC10 and nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β), and epidermal growth factor receptor expression. We found that HOXC10 expression increased in clinical samples, especially in poorly differentiated (PD) gastric cancer cells. Silencing HOXC10 suppressed proliferation, migration, and invasion in vitro, and inhibited tumor growth and induced apoptosis in vivo. Overexpression of HOXC10 showed the opposite effect on PD gastric cancer cells. In addition, silencing HOXC10 inhibited the expression of interleukin-6, TNF-α, TGF-β, and epidermal growth factor, and overexpressing HOXC10 induced their expression both in vitro and in vivo. Luciferase reporter assays and chromatin immunoprecipitation indicated that HOXC10 may activate the NF-κB signaling pathway through regulation of P65 transcriptional activity by binding to the P65 promoter. HOXC10 may play an important role in PD gastric carcinoma cell proliferation, cell cycle, migration, invasion, and metastasis through upregulating proinflammatory cytokines via NF-κB pathway, suggesting HOXC10 may serve as a novel therapeutic target for PD gastric cancer.

Role of HOXC10 in Cancer

“…( 51 ) found that high levels of HOXC10 in gastric cancer tissues were significantly associated with worse prognosis, as well as hepatic and peritoneal recurrence. And the studies confirmed that HOXC10 can cooperate with inflammatory cytokines ( 58 ), ATM/NF-κB axis ( 57 ), and EMT ( 60 , 64 , 65 ) to promote tumor migration and invasion. High HOXC10 expression can also induce tumor drug resistance by increasing DNA repair activity ( 52 , 53 ).…”

“…Li et al. confirmed that HOXC10 silencing suppressed metastasis and invasion, whereas HOXC10 overexpression significantly enhanced metastasis in gastric cancer cell lines ( 58 ). These studies suggested that HOXC10 may be a novel biomarker of metastasis, invasion, and recurrence after radical resection of gastric cancer.…”

“…Li et al. found that HOXC10 overexpression promoted metastasis and invasion by upregulating inflammatory cytokines in gastric cancer ( 58 ). In the tumor microenvironment, inflammatory factors, such as IL-6, TNF-α, and TGF-β, play an important roles in tumor occurrence, development, invasion and metastasis ( 85 ).…”

“…In the tumor microenvironment, inflammatory factors, such as IL-6, TNF-α, and TGF-β, play an important roles in tumor occurrence, development, invasion and metastasis ( 85 ). Mechanistically, HOXC10 could activates the NF-κB pathway by binding to the p65 gene promotor and indirectly upregulating inflammatory cytokines (IL-6, TNF-α, TGF-β, EGF) in gastric cancer cells ( 58 ). Interestingly, inflammatory factor IL-1β can also promote HOXC10 expression via the JNK/c-Jun pathway and induce invasion and metastasis of hepatocellular carcinoma ( 46 ), indicating that HOXC10 can promote tumor metastasis by cooperating with inflammatory cytokines.…”

HOXC10 promotes growth and migration of melanoma by regulating Slug to activate the YAP/TAZ signaling pathway

“…HOXC10 is a target of miR-129-5p, and miR-129-5p inhibits gastric cancer development by regulating HOXC10/Cyclin D1 axis [22]. HOXC10 is highly expressed in the poorly differentiated gastric carcinoma cells, and it accelerates proin ammatory cytokines through NF-κB signaling pathway to promote the progression of gastric carcinoma [23]. In liver cancer, HOXC10 expression is markedly decreased.…”