Purpose: This study was to investigate the clinicopathologic significance and potential role of HOXB7 in the development and progression of colorectal cancer (CRC).
Experimental Design: The relationship between HOXB7 expression and clinical characteristics of CRC was analyzed in 224 paraffin-embedded archived CRC specimens by immunohistochemistry (IHC). The effects of HOXB7 on cell growth and proliferation, as well as on tumorigenesis, were examined both in vitro and in vivo, using MTT assay, colony formation assay, cell cycle analysis, soft agar assay, and tumorigenesis in nude mice. Western blotting and real-time reverse transcriptase-PCR were performed to examine the impact of HOXB7 on the PI3K/Akt and MAPK signaling pathways.
Results: HOXB7 protein level was significantly correlated with advanced Dukes stage (P < 0.001), T stage (P = 0.012), distant metastasis (P = 0.042), higher proliferation index (P = 0.007) and poor survival of patients (P = 0.005). Enforced expression of HOXB7 in CRC cell lines significantly enhanced cell growth, proliferation and tumorigenesis. Conversely, knockdown of HOXB7 caused an inhibition of cell growth, proliferation, and tumorigenesis. We also showed that HOXB7 accelerated G(0)-G(1) to S-phase transition concomitantly with upregulation of cyclin D1 and downregulation of p27Kip1. On the contrary, knockdown of HOXB7 caused G(1)-S-phase arrest, downregulation of cyclin D1 and upregulation of p27Kip1. Enforced expression of HOXB7 could enhance PI3K/AKT and MAPK pathway activity.
Conclusion: Our findings suggest that HOXB7 protein, as a valuable marker of CRC prognosis, plays an important role in the development and progression of human CRC.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1158/1078-0432.CCR-10-2533 | DOI Listing |
JCI Insight
December 2024
INSERM UMRS 1131, Institut de Recherche Saint-Louis, Université Paris Cité, Paris, France.
Despite the advances in the understanding and treatment of myeloproliferative neoplasm (MPN), the disease remains incurable with the risk of evolution to acute myeloid leukemia or myelofibrosis (MF). Unfortunately, the evolution of the disease to MF remains poorly understood, impeding preventive and therapeutic options. Recent studies in solid tumor microenvironment and organ fibrosis have shed instrumental insights on their respective pathogenesis and drug resistance, yet such precise data are lacking in MPN.
View Article and Find Full Text PDFPharmaceuticals (Basel)
October 2024
Laboratório de Desenvolvimento de Sistemas Nanoestruturados, Faculdade de Farmácia, Universidade Federal de Juiz de Fora, Rua José Lourenço Kelmer, Juiz de Fora 36036-900, Brazil.
Background: Acquired resistance and adverse effects are some of the challenges faced by thousands of Luminal A breast cancer patients under tamoxifen (TMX) treatment. Some authors associate the overexpression of HOXB7 with TMX resistance in this molecular subtype, and the knockdown of this gene could be an effective strategy to regain TMX sensitivity. Therefore, we used calcium phosphate hybrid nanoparticles (HNP) for the delivery of short interfering RNA molecule (siRNA) complementary to the HOXB7 gene and evaluated the RNA interference (RNAi) effects associated with TMX treatment in breast cancer in vivo.
View Article and Find Full Text PDFNat Commun
October 2024
Genome Engineering and Model Development Lab (GEMD), IUF-Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany.
Sci Rep
September 2024
Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, No.6 Shuangyong Road, Nanning, 530021, Guangxi, People's Republic of China.
Evidences illustrate that cell senescence contributes to the development of pulmonary arterial hypertension. However, the molecular mechanisms remain unclear. Since there may be different senescence subtypes between PAH patients, consistent senescence-related genes (SRGs) were utilized for consistent clustering by unsupervised clustering methods.
View Article and Find Full Text PDFCancer Gene Ther
November 2024
National Center for Global Health, Istituto Superiore di Sanità, Rome, Italy.
We previously developed an innovative strategy to induce CD8 T lymphocyte-immunity through in vivo engineering of extracellular vesicles (EVs). This approach relies on intramuscular injection of DNA expressing antigens of interest fused at a biologically-inactive HIV-1 Nef protein mutant (Nef). Nef is very efficiently incorporated into EVs, thus conveying large amounts of fusion proteins into EVs released by transfected cells.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!