Tumor-suppressive function and mechanism of HOXB13 in right-sided colon cancer

Abstract

Right-sided colon cancer (RCC) and left-sided colon cancer (LCC) differ in their clinical and molecular features. An investigation of differentially expressed genes (DEGs) between RCC and LCC could contribute to targeted therapy for colon cancer, especially RCC, which has a poor prognosis. Here, we identified HOXB13, which was significantly less expressed in RCC than in LCC and associated with prognosis in RCC, by using 5 datasets from the Gene Expression Omnibus (GEO). Tissue sample analysis showed that HOXB13 was differentially expressed between normal and only RCC tumor tissues. HOXB13 inhibited colon cancer cell proliferation and induced apoptosis both in vitro and in vivo. Furthermore, we found that HOXB13 might be regulated by DNMT3B and suppress C-myc expression to exert antitumor effects via β-catenin/TCF4 signals in RCC. In conclusion, the current study is the first to demonstrate that HOXB13 has a tumor-suppressive effect in RCC. High expression levels of HOXB13 are associated with prolonged overall survival in patients with RCC. The DNMT3B-HOXB13-C-myc signaling axis might be a molecular target for the treatment of RCC.

HOXB13 suppresses proliferation, migration and invasion, and promotes apoptosis of gastric cancer cells through transcriptional activation of VGLL4 to inhibit the involvement of TEAD4 in the Hippo signaling pathway

“…Homeobox B13 (HOXB13) is an important member of the HOX family, which encode nuclear transcription factors that drive cell differentiation during normal development and tumorigenesis ( 4 ). HOXB13 has been reported to act as a tumor suppressor gene in a number of types of human cancer, including colon cancer ( 5 ), prostate cancer ( 6 ) and renal cell carcinoma ( 7 ). A previous study demonstrated that HOXB13 expression was significantly downregulated in primary GC tissues compared with the corresponding non-malignant gastric tissues, and HOXB13 expression was positively correlated with the 5-year overall survival rate ( 8 ).…”

Long Noncoding RNA HOXA11-AS and Transcription Factor HOXB13 Modulate the Expression of Bone Metastasis-Related Genes in Prostate Cancer

“…In this study, we identified HOXB13 as an upstream transcriptional regulator of HOXA11-AS in human bone metastatic prostate PC3 cells. Deregulation of HOXB13 expression has been implicated in a variety of other human cancers, functioning as a tumor-promoting factor in some tumor types and a tumor-repressing factor in other tumor types [ 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ]. Within the context of HOXB13-associated binding partners, HOXB13 may provide specificity for DNA binding and subsequent tumor progression or repression.…”

HomeoboxC6 promotes metastasis by orchestrating the DKK1/Wnt/β-catenin axis in right-sided colon cancer

“…Given that canonical driver mutation genes such as APC , TP53 , and KRAS are shared by LCC and RCC, it is tempting to believe that activation of specific oncogenes and/or silencing of tumor suppressors may better explain their prognostic difference and also provide clues for treatment. Recently, HOXB13, another member of the homeobox gene family, was found to be downregulated in RCC via hypermethylation and to play a tumor suppressive role in RCC 20 . However, HOXC6 was confirmed to be overexpressed in RCC and associated with poor prognosis in this study, which is in line with previous studies in other cancer types 11 , 21 , 22 .…”